Posts Tagged Depression

[ARTICLE] Epilepsy Benchmarks Area I: Understanding the Causes of the Epilepsies and Epilepsy-Related Neurologic, Psychiatric, and Somatic Conditions – Full Text


The 2014 NINDS Benchmarks for Epilepsy Research included area I: Understand the causes of the epilepsies and epilepsy-related neurologic, psychiatric, and somatic conditions. In preparation for the 2020 Curing Epilepsies Conference, where the Benchmarks will be revised, this review will cover scientific progress toward that Benchmark, with emphasize on studies since 2016.

Introductory Vignette by Lizbeth Carmichael. Epilepsy, Depression, and SUDEP—A Parent’s Perspective

My son John developed epilepsy in his late teens, and despite medications, his seizures remained severe and uncontrolled. John was a talented and creative musician and a caring and thoughtful brother and son. He had many friends, and he desperately wanted an independent life. As John’s epilepsy progressed, he also experienced declining mental health. John, who was normally a very peaceful individual, had periods of severe irritability and rage. He also became very anxious at times, and this was a sign of an impending seizure. John heard voices and developed paranoia, hallucinations, and depression. Our family was told to see specialists, but we found that the communication and coordination of care between epileptologists and mental health professionals was impossible, even when he was hospitalized and referrals were made. Ultimately, his mental health issues were not understood or addressed and contributed significantly to his decline. John died of sudden unexpected death in epilepsy (SUDEP) in 2012. Our family’s wish is that those around John had been more attuned to the mental health comorbidities that he was experiencing, and that his medical issues were jointly managed as the outcome for him might have been different.

Significant comorbidities often accompany epilepsy and can be more debilitating than the seizures themselves. A better understanding of the underlying mechanisms of epilepsy-associated comorbidities and appropriate clinical care is critical for increased quality of life for those impacted by epilepsy and their families.

Lizbeth Carmichael. Forever John’s Mom. Citizens United for Research in Epilepsy (CURE).


In this review, we provide an update on preclinical and clinical advances into our understanding of the many etiologies of the epilepsies, as well as progress in assigning etiology to epilepsy-related neuropsychiatric and somatic comorbidities. Since the most recent summary in this area,1 expansion in our knowledge of epilepsy genetics and autoimmune epilepsies has continued to result in fewer individuals being labeled with epilepsy of unknown etiology. With the advent of next-generation sequencing technologies, the number of “epilepsy genes” continues to expand. Assigning a causative role to such genes requires verification in not only larger cohorts with statistical rigor but also a number of criteria that take into account normal variation, determination of how a genetic change leads to altered molecular function, and the demonstration of an epilepsy or epilepsy-related phenotype in genetically manipulated model organisms.2 Similar considerations apply for autoimmune epilepsies, for which the relative epileptogenic effects of T-cell infiltration and circulating antibodies continue to be clarified.

Preclinical models of genetic, autoimmune, and brain injury-related epilepsies have been essential to advance our knowledge into upstream and downstream cellular and neurophysiological perturbations that may promote hypersynchrony and the transition to the ictal state. It is only with this type of knowledge that we will be able to better inform treatment of epilepsy related to these types of epilepsy. Incomplete penetrance and variable phenotypes in both humans and animal models strongly implicate genetic modifiers of susceptibility, which need to be identified and validated so as to appreciate mechanisms by which epilepsy may be therapeutically modulated.

In parallel with efforts to address the causes of epilepsy and epileptogenesis, there has been an expansion in efforts designed to unravel the genesis of epilepsy’s various psychiatric comorbidities. Generally, these are etiologically related to broad network dysfunction that may be secondary to the underlying epileptogenic lesion (genetic, structural, or unknown) and actively modulated by the burden of ongoing seizures (if present) and antiseizure medications. Animal models of monogenic epilepsies provide the most tractable route to assigning etiology to epilepsy-associated comorbidities, albeit with some limitations in the ability to assess psychiatric comorbidities in various models. Incorporating optogenetic and chemogenetic strategies in these models affords the ability to definitively test whether specific network abnormalities affect seizure risk or impact limbic function or cognitive function or both.

We conclude our review with a set of general recommendations for future research into the causes of epilepsy spectrum disorders that will guide our understanding into epilepsy prevention (area II), treatment options (area III), and the adverse consequences of seizures themselves (area IV).

Key Advances in Area I

Epilepsy Genetics

Advances in our understanding of the genetics of the epilepsies have continued to accrue since the last Benchmarks update and have been reviewed in several excellent publications.36 Many new variants associated with epilepsy are identified as “de novo dominant,” meaning that they are present in the heterozygous state in sporadically affected individuals. At a cellular level, these genes encode proteins that display a broad range of functions that extend well beyond ion channels, including cell adhesion (eg, PCDH19), DNA binding and chromatin remodeling (eg, CHD2), and neurotransmitter release (eg, STXBP1).7 The importance of genetic etiologies in focal epilepsy in particular has become even more clear, with the involvement of DEPDC5 and associated GATOR1-complex mTOR repressors in epileptogenic cortical malformations being notable examples.8

De novo postzygotic (somatic) mutation has been increasingly recognized to play a role in focal epilepsy, largely involving the mTOR pathway in the pathogenesis of lesional epilepsies such as focal cortical dysplasia and hemimegalencephaly, with a majority of cases explained by this mechanism.911 Extending the discovery of somatic mutation to a new pathway and, interestingly, to both focal cortical dysplasia (type I) and nonlesional focal epilepsy was a report on mosaic variants in the gene SLC35A2, which encodes an UDP-galactose transporter previously associated in nonmosaic form with developmental and epileptic encephalopathy.12 The discovery of these 2 distinct pathways may point to very different targeted therapies after further study, which is promising but also demands attention to precision in classifying individuals with focal epilepsy and establishing a molecular diagnosis before pursuing experimental therapy.

Although most newly discovered pathogenic variants each seem to be causative in only a small number of individuals, taken together their combined impact is substantial. From the perspective of practicing epileptologists, we now benefit from a relatively high rate of identifiable genetic causes in neonatal and early childhood epilepsies, particularly in those individuals with comorbid intellectual disability, so that more routine usage of next-generation sequencing methods in this population may be warranted.13,14 Much more research is needed, however, to separate out the effects of seizures, genetic changes, and treatments on the intellectual impairments that are found in the epileptic encephalopathies.15

Animal models have permitted important insights into the specific mechanisms by which genetic aberrations may promote hyperexcitability. In additional to conventional “knockout” mice, mutants with conditional gene deletions (permitted via Cre-LoxP technology) have helped dissect the individual contributions of specific neuronal populations to seizure generation. For example, mice with a conditional deletion of Lgi1 in parvalbumin-positive interneurons alone are devoid of spontaneous seizures, while conditional deletions of Lgi1 in forebrain glutamatergic neurons result in frequent early-life seizures and premature death,16 just as in Lgi1 knockout mice.17 These results not only provide guidance to future gene replacement strategies but also show that while Lgi1 is an extracellularly secreted protein that is expressed in both GABAergic and glutamatergic neurons, restoring Lgi1 expression in glutamatergic neurons may be more likely to ameliorate seizures. The lack of spontaneous seizures in mice with heterozygous deletions of Lgi1 (recapitulating the haploinsufficiency of LGI1 mutation-related lateral temporal lobe epilepsy [TLE]) illustrates an important point with regard to gene dosage in animal models. Similar findings exist with other epilepsy genes, including KCNQ2,18 CDKL5,19 and DEPDC5. 20 Heterozygous DEPDC5 variants are found in cases of familial focal epilepsy as well as focal cortical dysplasia–associated epilepsy.20,21 Mice or rats with homozygous germ line deletions of Depdc5 had embryonic lethality,2224 which is itself etiologically nonspecific and may even reflect placental pathology.25 In contrast, rats with heterozygous deletions of Depdc5 do not display spontaneous seizures.24 Mice with a conditional brain-specific homozygous deletion of Depdc5 display extremely rare seizures, together with macrocephaly, impaired survival, and biochemical evidence of mTOR1 complex activation.22 Thus, it appears that for certain genetic variants strongly associated with epilepsy in humans, mice with corresponding gene deletions or transgenic “knock-ins” of variants seen in individuals with the specific epilepsy syndrome may not display spontaneous seizures or even reflex audiogenic seizures, a common expression of epilepsy in mice. This phenomenon may reflect the influences of variations in genetic background or fundamental differences in mechanisms of genetic epileptogenesis between mice and humans.

Confirming the epilepsy-inducing or epilepsy-modifying effects of specific variants may be greatly aided through the use of other vertebrate models, such as zebrafish (Danio rerio). Classically employed as a model to study embryology and development, zebrafish has now been adopted to study a variety of neurological disorders, including epilepsy. This species is amenable to exon deletion via homologous recombination, and specific single-nucleotide variants can be introduced via CRISPR-Cas9 technology.2628 As with mice, stereotyped spontaneous or induced seizures can be identified by video tracking and/or electroencephalography. The small size and rapid development of zebrafish also permit high-throughput drug screening29 that may be individualized to identify a treatment for a specific variant.30

Despite the impressive array of genetic advances, the translation of these findings into gene-related or pathway-based clinical treatments has had mixed results.31 There are genetic diagnoses for which specific antiepileptic therapies are either indicated or relatively contraindicated (eg, GLUT1 deficiency, pyridoxine dependency, SCN1A-related epilepsy), and mTOR inhibitors are now known to be at least partially effective for tuberous sclerosis complex–associated epilepsy.32 By contrast, the use of quinidine for KCNT1-related epilepsy, initially thought to be promising following the report of a single case,33 has not been shown to reduce seizure frequency in subsequent studies.34 Overall, these and other findings suggest that simply modulating a causative pathway featuring a rational drug target can lead to variable responses. More work is clearly necessary to bring genetic discoveries from the bench successfully to therapeutic application at the bedside.

Interneuronopathy-Related Epilepsies

Interneuronopathies can be broadly defined as those conditions in which epilepsy or neuropsychiatric comorbidities arise as a consequence of either developmental or functional changes in interneurons. Alterations in interneuron migration or numbers have been identified in multiple epilepsy mouse models, including mice with deletions of Cntnap2,35 Wwox,36 and Syngap1,37 as well as in certain models of acquired epilepsy,38,39 and after traumatic brain injury.40,41 Epilepsy that occurs in Dravet syndrome associated with pathogenic variants in SCN1A may also be classified in this category based on evidence that interneurons in Scn1a heterozygous mice display a selective decrease in excitability, and selective deletions of Scn1a in interneurons are sufficient to recapitulate the spectrum of Dravet-related phenotypes.4244 The term “interneuronopathy” was first used in the setting of a very severe genetic epilepsy syndrome (X-linked lissencephaly with ambiguous genitalia, XLAG) caused by pathogenic variants in ARX, with significant reductions in interneuron density in hippocampal and cortical regions observed in this condition.4547

A more detailed understanding of interneuron development and migration patterns will be critical for developing novel treatments for these specific genetic epilepsy syndromes and will guide our explorations into the therapeutic potential of either transplantation48,49 and/or optogenetic/chemogenetic manipulations of interneurons.

Tumor-Related Epilepsies

The incidence of epilepsy in individuals with brain tumors ranges from 70% to 80% in glioneuronal tumors (including gangliogliomas and dysembryoplastic neuroepithelial tumors) to 20% to 35% in individuals with brain metastases.50 Epileptogenesis associated with gliomas, the most common malignant primary brain tumor, has been a focus of intense research, with 2 nonmutually exclusive mechanisms explored extensively.

For some neurodevelopmental tumors such as ganglioglioma, a genetic profile has become apparent in the form of a BRAF V600E variant, suggesting the possibility of treatment with BRAF inhibitors.51 Furthermore, in some tumors, malignant glial cells release excessive amounts of glutamate through the cystine/glutamate transporter (SLC7A11), a gene whose expression is upregulated in at least half of all glial tumors.52 SLC7A11-mediated glutamate release results in hyperexcitability that spreads to adjacent tissues,53 and in preclinical studies, a currently available SLC7A11 inhibitor (sulfasalazine, utilized in the treatment of Crohn disease) resulted in improved seizure frequency and prolonged survival.54 Mutations in isocitrate dehydrogenase (IDH1) are a strong predictor of epilepsy in patients with low-grade glial tumors.55 Mutant IDH1 converts isocitrate to 2-hydroxyglutarate (instead of α-ketoglutarate), which is structurally similar to glutamate and sufficient to lengthen burst duration in cultured rat cortical neurons in an NMDA-receptor-dependent fashion.55

A second potential mechanism involves the dysregulation of chloride homeostasis in peritumoral cortical neurons through the aberrant downregulation of KCC2 (potassium chloride cotransporter) and upregulation of NKCC1 (sodium potassium chloride cotransporter) within these cells.56 Under these conditions, γ-aminobutyric acid (GABA) binding to ionotropic receptors results in depolarization, and inhibitors of NKCC1 (which reverse altered chloride gradients) in preclinical glioma models improve seizure susceptibility.57 It remains to be seen whether similar mechanisms of epileptogenesis may be involved in epilepsies related to meningiomas or metastatic lesions, for which preclinical models are less well developed. Clearly, cortically based or invading tumors seem to possess the greatest risk of epilepsy.50

Autoimmune Epilepsies

As of 2019, antibodies to at least 11 different antigens have been associated with epilepsy occurring in the context of encephalitis. Antibodies against extracellular antigens raise neuronal excitability and impose synaptic dysfunction either by disrupting specific protein interactions (eg, LGI1, NMDAR), enhancing receptor internalization (AMPAR), or by functioning as an antagonist (GABA-BR).58 In contrast, antibodies against intracellular antigens are thought to produce epilepsy as a consequence of direct cytotoxic T-cell infiltration (eg, amphiphysin, GAD-65). The clinical presentation of autoimmune encephalitides is highly variable (signs and symptoms of limbic or motor dysfunction may or may not be present), and seizures may be the presenting symptom, a late symptom, or absent entirely.59

Establishing a direct causative link between individual antibodies and their specific mechanisms of epileptogenesis has been possible through experiments in which patient-derived antibodies are infused into mouse or rat models. For example, hippocampal specimens from mice that received intracerebroventricularly infused LGI1 antibodies over 14 days displayed reduced synaptic expression of the voltage-gated potassium channel KV1.1 (KCNA1) together with increases in presynaptic-release probability and postsynaptic current amplitudes, as well as diminished long-term potentiation and impairments in learning and memory.60 These mice did not develop spontaneous seizures, suggesting that at least in mice, either longer durations of anti-LGI1 antibody exposure or higher antibody titers may be necessary for seizure generation. In contrast, similar infusions of anti-NMDAR antibodies in mice produced spontaneous seizures without impairments in memory or motor function.61

Recent genome-wide association studies have revealed that particular human leukocyte antigen (HLA) haplotypes may increase the risk of specific antibody-mediated encephalitides,59,62,63 just as with other autoimmune conditions such as type I diabetes mellitus or ankylosing spondylitis; these HLA associations provide pathophysiological insights into the genesis of these antibodies. Fortunately, only a minority of patients who display acute symptomatic seizures during active encephalitis go on to develop epilepsy.58 Early immunomodulatory therapy appears to be critical to avoid future drug resistance, while other factors, such as medical complications or hypoxia, may also contribute to long-term seizure risk.58,59

Epilepsy-Related Conditions

Adults have a median of 2 chronic medical conditions, but this number rises to 6 in individuals older than 65 years.64 Thus, “comorbidities” are a central aspect of all chronic medical conditions, and epilepsy is no exception. In epilepsy, comorbidities can be broadly divided into those which affect mental health (including sleep), general physical health (including trauma), and reproductive health.65,66 Together, these comorbidities contribute tremendously to overall disability, impairments in quality of life, and premature mortality.67,68 Outside of chance or artifactual comorbidities that may reflect various forms of bias,64 4 main mechanisms of comorbidity have been proposed69: (1) independent comorbidity (etiologically unrelated to epilepsy), (2) consequent comorbidity (a direct consequence of epilepsy), (3) iatrogenic comorbidity (treatment related), and (4) shared risk factor (in which epilepsy and its comorbidity independently arise from a single etiology). Importantly, shared risk factors may epidemiologically resemble a bidirectional association (in which each condition causes the other).

Psychiatric comorbidities in epilepsy have received the greatest emphasis. Epilepsy is associated with significantly higher rates of mood and anxiety disorders,70,71 psychosis,72 fatigue,73 and autism spectrum disorder.74 These entities are each independently associated with varying degrees of intellectual disability. Cross-sectional and/or prospective human data provide a framework for mechanistic hypotheses into their etiology; ultimately, these hypotheses require verification in animal models. Unfortunately, this schema is inherently limited since many psychiatric endophenotypes are either absent entirely (eg, suicidality) or difficult to measure (eg, depressed mood, psychosis) in animal models.

Depression, or major depressive disorder, has and will continue to be a major focus of comorbidity research. Individuals with epilepsy are twice as likely to develop depression over their lifetime,70 and either entity can occur first.75 The severity of depression is associated with the risk of epilepsy.76 Depression and suicidality tend to be more prominent in individuals with TLE compared with those who have genetic generalized epilepsies,77,78 and within TLE, depression severity correlates with pharmacoresistance but does not correlate with the side57 or the extent of hippocampal atrophy,79 if present. Improvements in depression that follow temporal lobectomy are strongly associated with improvements in seizure control.80 To date, there has been no high-quality evidence to suggest that antidepressants (in conjunction with standard anticonvulsant therapy) are sufficient to either impact epilepsy risk or reduce seizure frequency.81 On the other hand, behavioral interventions such as cognitive behavioral therapy or mindfulness training have been shown to improve both seizure control and quality of life.82 Overall, this body of evidence argues strongly for the presence of shared noniatrogenic neurobiological risk factors that simultaneously raise the risk of depression and epilepsy.

What are these risk factors? Genetic or epigenetic factors may play only a modulatory role since major depression and epilepsy display little to no evidence of genetic overlap (unlike autism and epilepsy).78 The roots of epilepsy–depression comorbidity may be related to changes in network functional connectivity. In major depression, such functional rearrangements are broad, bilateral, and vary by depression subtype.83,84 At least within TLE circuits,85 hyperexcitability within the anterior hippocampus (corresponding to the ventral hippocampus in rodents) may be one such anatomical substrate for comorbidity. In mice, ventral hippocampal injections of kainic acid produce epileptic seizures together with memory impairments and anhedonic behavior; these behavioral comorbidities were not observed in mice that received dorsal kainic acid injections.86 Hypersynchrony in the anterior/ventral hippocampus region may contribute to depressive symptoms by compromising functional connectivity to ipsilateral frontal regions.87

Testing these hypotheses in preclinical models is now possible with optogenetics, in which an anatomically or molecularly defined neuronal population is genetically or virally transduced to express an excitatory or inhibitory ion channel that is activated by light of a specific wavelength. Bilateral optogenetic activations of ventral hippocampal afferent pathways in nonepileptic mice are sufficient to produce depression and anxiety-like symptoms.88,89 Similarly, the optogenetic inhibition of mossy cells within the dentate gyrus (simulating mossy fiber loss) is sufficient to produce impairments in object memory in mice.90 Aside from these focal network derangements, aberrations in a variety of other neuromolecular axes have been proposed as substrates that may raise seizure risk and compromise mood, including disturbances in neurotransmitter signaling (glutamate, GABA, serotonin), dysfunctional hypothalamo–pituitary–adrenal axis signaling, and a host of cellular and secreted mediators of neuroinflammation.57,91

Looking Forward: Opportunities and Challenges

Given the progress over the past several years and the remaining gaps in knowledge in the field, we have identified some ambitious but feasible future priorities in epilepsy research that we believe should guide our scientific efforts in this area over the next decade. First, it is notable that a large portion of this update has been devoted to genetic advances, given the substantial work in this area. We also recognize that many patients worldwide have epilepsy primarily caused by infection, head injury, birth trauma, hypoxic–ischemic insult, or any of a number of other perturbations of nervous system function. We support an increased focus on investigating the underlying causes and mechanisms of all forms of epilepsy, including these acquired forms of epilepsy, in order to improve our ability to prevent and treat these conditions successfully.

We also support further work on the cognitive and behavioral deficits that accompany epilepsy through experimental animal models, including further use of chemogenetic and optogenetic strategies to study specific cellular populations in the pathogenesis of epilepsy and related conditions. An important question with direct clinical relevance centers on the transition to the ictal state: Since seizures occur only in discrete episodes in most instances, we need a better understanding of what allows them to arise at any particular time and what limits transition to an ictal state at other times.92

We support continued attention on interneuron pathology, central neuronal signaling pathways, and autoimmune factors as underlying mechanistic factors in both genetic and acquired epilepsy syndromes. Further, invoking another less well-studied cell type in the nervous system, we support evaluation of the role of glia in epileptogenesis and seizure propagation. The pathogenesis of infection-related epilepsy, including virus-induced epilepsy and parasite-induced epilepsy, the latter of which is a leading cause of epilepsy worldwide but lacks a relevant animal model, needs further exploration. In general, the links between the brain and immune system and the relationship between inflammation and neural excitability should be critical targets of investigation. Despite the large volume of new advances in epilepsy genetics, we believe there needs to be further characterization of genes associated with the most prevalent early-life syndromes and further research on the use of “rational” therapy design to modulate known pathogenic pathways.

Although some work has been devoted to understanding the causality behind some of the most common epilepsy-related comorbidities, much more is required. We would support further research aimed at disentangling the effects of seizures, genetic changes, and antiseizure medication in contributing to the intellectual impairments that are present in patients with epileptic encephalopathies. In addition, we believe that further timely study of epilepsy etiologies in elderly individuals, who represent a second peak of epilepsy incidence after early childhood, could be highly impactful. Recent findings related to hippocampal hyperexcitability in individuals with Alzheimer disease93 and the discovery of associations between lifestyle risk factors and late-onset epilepsy94 provide tantalizing suggestions of important etiological connections in older adults who had multiple medical conditions.

“Doctor, what is causing my seizures?” At the current time, in a significant majority of individuals, including those without a definite brain lesion, an encephalitic prodrome, evidence for a familial epilepsy syndrome, or a comorbid neurodevelopmental syndrome, the answer to this question remains unknown. Fortunately, 65% of individuals will experience seizure freedom with 1 or more currently available antiseizure medications.95 To improve the lives of all individuals affected by epilepsy, however, we must address the fundamental causes of epilepsy and its associated conditions. As demonstrated in the introductory vignette, we also have a responsibility to translate our scientific advances toward the treatment of epilepsy and fcognitive and psychiatric comorbidities in a coordinated fashion.


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[Abstract] Effects of Seizure Frequency, Depression and Generalized Anxiety on Suicidal Tendency in People with Epilepsy


  • Seizure frequency was positively associated with suicidal tendency.
  • Depression mediated the relationship between seizure frequency and suicidal tendency.
  • Generalized anxiety moderated the effect of seizure frequency on suicidal tendency.



The highest risk of suicide was identified among patients diagnosed with both epilepsy and comorbid psychiatric disease. The most common comorbid psychiatric conditions of epilepsy are anxiety and depression. This study examines whether and how seizure frequency, depression and generalized anxiety interact to influence suicidal tendency.


A consecutive cohort of PWE was recruited from the First Affiliated Hospital of Chongqing Medical University. Each patient completed the Neurological Disorders Depression Inventory for Epilepsy scale[NDDI-E], the Generalized Anxiety Disorder-7 (GAD-7), and the suicidality module of Mini-International Neuropsychiatric Interview(MINI) v.5.0.0. Spearman’s correlation and moderated mediation analysis were used to examine the associations among seizure frequency, depression, generalized anxiety and suicidal tendency.


Seizure frequency was positively associated with suicidal tendency. Depression severity partially mediated the relationship between seizure frequency and suicidal tendency. The indirect effect of seizure frequency on suicidal tendency was positive, and accounted for 50.2% of the total effect of seizure frequency on suicidal tendency. The indirect effect of seizure frequency on suicidal tendency through depression severity was positively moderated by generalized anxiety severity.


Reducing seizure frequency may be the basis of suicide prevention in PWE. At the same time, the effect of seizure frequency on suicidal tendency can be partially explained by the mediation of depression severity, and the magnitude of the indirect effect of seizure frequency on suicidal tendency was contingent upon generalized anxiety severity. In addition to depression severity, generalized anxiety severity also exerts an important effect on suicidal tendency in PWE.

via Effects of Seizure Frequency, Depression and Generalized Anxiety on Suicidal Tendency in People with Epilepsy – ScienceDirect

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[BLOG POST] The Difference Between Depression and Sadness

As our society grows and we are slowly beginning to destigmatize mental health, one of the most common and discussed mental illnesses is depression. And while it’s great that we are slowly starting to have open conversations, I fear there is a misunderstanding when it comes to what depression really is.

When people think of depression, they tend to associate it with sadness. For the record, let’s make something incredibly, ridiculously, absolutely crystal clear. Sadness is an emotion. Depression is a clinical mental illness.

Everybody is bound to experience sadness at some point. Whether it’s a disappointing test score, a friend’s betrayal or a heart-wrenching breakup, you will feel sad. But then you’ll feel better. And you’ll move on with your life and be bigger and better. You’ll feel sad, but you won’t necessarily be depressed.

Depression is a clinical illness. It’s been scientifically proven and documented that depression has a literal, physical effect on your brain. No ifs, ands or buts.

Depression is not just feeling sad.

In fact, it’s not feeling… anything. At all.

It’s the feeling of numbness, a sense of nothingness.

It’s the feeling of “why”… about everything.

Existential crisis after existential crisis.

Being sad and being depressed are not the same thing. Next time you’re feeling down, please still try to be wary of your words. If you’re sad, you’re sad. If you’re depressed, you’re depressed. Both are equally valid and equally important but don’t throw around “depression” like a colloquial phrase. It’s not meant to help you emphasize a point. It’s a mental illness. We have a hard enough time as is, please do not make it any harder by making it invalid – in your eyes and in the eyes of others.

Depression is not something we just “get over”.

Depression is nothing something that a pint of ice cream and a funny movie can fix.

Depression is a mental illness.

Depression is not sadness.

Lead Image From Thinkstock


via The Difference Between Depression and Sadness | The Mighty

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[WEB SITE] If You Have an Acquired Disability, Resist the Urge to Isolate Yourself, Kessler Expert Advises

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Helen M. Genova, PhD, assistant director of the Kessler Foundation’s Center for Neuropsychology and Neuroscience Research and director of the Social Cognition and Neuroscience Laboratory, shares her thoughts on how dealing with an acquired disability can affect someone mentally and physically.

What are the emotional effects an acquired disability can have on an individual?

People who have an acquired disability may have a number of emotional issues — physical and mental changes that may raise the risk for depression and anxiety. For example, people who have typically led an active lifestyle may find new physical limitations challenging in designing a new exercise program. Some individuals (like those with multiple sclerosis or a traumatic brain injury) may experience cognitive symptoms, such as memory problems, learning problems or severe fatigue, which make it difficult to spend time with friends or attend family holiday festivities. All of these symptoms may lead to depression, or make preexisting depression worse.

Are people with acquired disabilities more prone to loneliness than non-disabled individuals?

Unfortunately, people with acquired disabilities may be more prone to loneliness for a number of reasons. For one, they may experience new physical and mental limitations that may not allow them to lead the life they want to lead. For example, someone who had a career and an active social life before their diagnosis may find it difficult to “keep up” with their old way of living, because they are too fatigued to participate in life the way they used to, or they physically cannot perform the same activities they use to perform. This may lead to social isolation and loneliness. Further, some people with disabilities isolate themselves from others because they do not want to be a “burden” to their families and friends. They may feel that their disability is an inconvenience to others, or tire of having to explain why they are not feeling well, need to cancel plans, or leave early, etc. These feelings may lead them to avoid social interaction altogether, which only leads to more loneliness, and a cycle that can be difficult to break.

What advice would you give to people who are living with an acquired disability and experiencing feelings of loneliness (especially during the holidays)?

I recommend that they resist the urge to isolate themselves. In other words, find good friends who understand their disability and can provide unconditional support. Another option is to find support groups or classes geared towards people with similar disabilities. Spending time with people who truly understand what they are going through can be very comforting. Realizing that others are experiencing similar life struggles may reduce feelings of loneliness, and help you to feel more connected to others.

 [Source(s): Kessler Foundation, PRWeb]


via If You Have an Acquired Disability, Resist the Urge to Isolate Yourself, Kessler Expert Advises – Rehab Managment

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[WEB SITE] The Parts of Epilepsy We Often Don’t Talk About


Growing up, my biggest secret was that I had epilepsy. I have had it since I was 5.  Neurologists kept saying, “She’ll grow out of it.” I’ve tried medication after medication, trying to control the seizures and limit the number of side effects.  I’ve tried weaning off medication, only for a seizure to return within one or two days. Life becomes more bearable when my seizures are controlled, but I never feel carefree.  Epilepsy is much more than having seizures.

With my epilepsy comes fear.  I am constantly cautious and afraid.  I am afraid of having a seizure during school, at work or in public.  Although I’ve been seizure-free for over a year, I am afraid of driving down the road and feeling that tingling in my stomach and not being able to pull the car over quickly or safely enough. I am afraid of injuring my brain and body beyond repair. I am afraid of who will see me. I am afraid of waking up from a seizure and being alone. I am afraid of forgetting my medication.

With my epilepsy comes depression. For me, epilepsy has always brought along depression for company. With each anti-seizure medication, the depression waxes and wanes, but it always lingers like a permanent resident in my brain.  When I am honest about my suicidal thoughts, doctors prescribe an antidepressant. We both hope the depression will fade, but I am usually met with a new set of side effects.  Together, both conditions appear invincible, but I always fight back. Depression tells me to die instead of taking the pills from the container. Depression tells me the darkness is here to stay.  Depression steals my energy and my smiles. When I am always outnumbered, and the fight is unfair, I wonder how much of who I have become is due to the medication and how much is truly me.

Too often, with epilepsy comes shame. All through grade school, I heard kids at school make fun of seizures and even pretend to have seizures. I listened and watched. As one of the quietest students in class, my lips felt zippered shut, but my face turned red. They did not know what it feels like to lose control of your body. They didn’t know what it was like to wake up confused and disoriented, not knowing how long the seizure lasted or what was happening before it. I was not brave enough to speak up.

My closest friends didn’t know I had epilepsy. I snuck away at sleepovers to take my medication at 8:00 p.m. I made excuses as to why I couldn’t drive, why I wouldn’t drink alcohol, why I occasionally arrived to school late, why I visited a hospital that was over an hour away rather than the local doctor’s office, or why there was a bruise on my forehead.  When I started telling people outside of my family, they would reply with phrases such as “I didn’t know that you were an epileptic,” “I need to be careful around you,” or “At least it’s not something terminal.” They may not have known their words were insensitive or hurtful, but I have never been met with comfort or acceptance after telling my story. Only shame.

Epilepsy can be somewhat of an invisible illness. Sometimes I can hide it. Other times, I can’t. Epilepsy is much more than having seizures.  For some people, myself included, it’s a lifelong challenge.

Having epilepsy can mean battling depression, anxiety, insomnia, muscle weakness, lethargy, weight gain, and a host of other negative side effects from seizures and medications. It can mean staying home from work or school because of an aura. It can mean keeping secrets from best friends. It can mean refusing to give up regardless of what others think and say, how many medications you’ve tried, and the side effects that never subside. I have often wondered who I would be without epilepsy. While I fight the shame and stigma within myself, I have learned and accepted that epilepsy is a part of who I am.

But only one part.


If you or someone you know needs help, visit our suicide prevention resources.

If you need support right now, call the National Suicide Prevention Lifeline at 1-800-273-8255, the Trevor Project at 1-866-488-7386 or reach the Crisis Text Line by texting “START” to 741741.

via Epilepsy Is About More Than Seizures | The Mighty

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[QUOTE] 21 Positivity Quotes to Help You Beat Depression



Depression signs often come in multiple episodes. You might feel like you have won, but you find yourself in another panic attack. Fast forward, a round of anxiety can follow the later depression episode.

However, F. Scott Fitzgerald encourages you to keep moving forward. In his quote, he states that you should never get discouraged in fighting depression. He reassures you by saying that a single setback should not deter you from building resilience to fight your mental illness.
Confucius encourages you to be resilient in fighting depression. Falling on the way is just a setback. Your success in overcoming depression is your ability and strength to recover from a low day and anxious week. Your success is in moving forward.

According to Buddha, you should forget yesterdays panic attack and always start fresh. You must forget your worries and move forward. Each morning is branded as a new chance for you to feel better and become stronger. Therefore, each day presents you an opportunity to gather your mental strength and maintain emotional stability.

Depression is a complex mental illness that affects your daily well-being. Beating it encompasses immense procedure that requires total involvement. Depression presents you with an insurmountable task, ranging from dealing with depression to anxiety regardless of your emotional strength.

Confucius’s quote inspires you to keep fighting the depression battle. The fact that slow or straightforward progress can gradually produce enormous results reassures you when you are weak, tired, and low.

According to Christian D. Larson, depression is a battle that requires inner strength. The first step to beating depression and anxiety is accepting that you have the will and power to do it. Self-believe can give you the bravery to move forward and win.

We become stronger by being resilient in the battle against depression. Those who have beat depression before have a deeper understanding and compassion that makes them sensitivity about its causes.

Elisabeth Kübler-Ross encourages victims not to shy away from acknowledging our secret battles. Instead, victims should be proud of the work we put into beating our mental illness.

To overcome depression is a complex process that requires patience. Therefore, pushing yourself too hard and very quickly can cause you more harm. Take it slow, and you will overcome the challenge you encounter as you progress

St. Francis of Assisi states that today’s problems can be tomorrow’s strengths. Thus, you should never give up because something seems impossible today.

According to Thich Nhat Hanh, the battle of depression is a continuous process that can never end. Every day presents new mental challenges. You must give yourself space to face your challenge slowly. Therefore, breath, pose, have fun before you continue.

Depression can push you into deep thoughts that can be unwanted. The biggest challenge can be if you let your ruminations control you. Dan Millman inspires you not to give up if you fail to control your thoughts. He encourages the depressed by telling them that they have the power to determine how their thinking can affect their emotions and responses.

10 – “Learn from yesterday, live for today, hope for tomorrow.” -Albert Einstein

You must keep your hope alive if you want to win the depression battle. You should stop dwelling in the past and face the present head-on. According to Albert Einstein, hoping for tomorrow can help you from preventing recurring depressive episodes and future anxiety relapses.

To overcome depression, you must train your mind to hope for a brighter future. By focusing your mind on a positive future, it helps you overcome the darkest moments from your past. Always hope for a bright future and your fears and anxieties cannot push you to depression.

Depression can drive you crazy at times. It can take up most of the persons’ daily life. Julian Seifter encourages you to be honest with your mental illness and believe that it does not define personality.

Depression destroys lives. It can make you second guess yourself and mental state. However, loving yourself is the first step towards accepting and implementing effective ways of overcoming the problem.

Hold on to the hope of a better future even when the day seems gray in their minds. John Green’s inspiration quote can uplift a person who is feeling down by helping them control their emotional responses.

The worst bit of battling depression is when people lose their self-worth. They withdraw from the conventional world. However, a simple reminder of their goodness can be what they need to keep moving forward.

Dodie Smith believes that instead of feeling depressed, you should spend more time giving back to society. She bases his concept on the fact that you elevate your self-worth whenever you help a person in need. So, take a little time out for self-care. You earned it!

A depressed person should always remember that they should strive to regain control of their emotions. They should never let their minds determine their actions. A small reminder of this vital truth can uplift you from your depression state.

The best way to fight depression is understanding its root causes. Gilbert Baker points out that faking your lifestyle is a cause of depression that you should never let take over your life. Instead, stay true to your values, and you will live a stress-free experience.

Depression is often caused by dwelling in the past events and thought. Amit Ray, in Om Chanting and Meditation believes that unless you are ready to let go of the past, you are not prepared to battle what is depressing you.

You can draw your inspiration from Dorothy M. Niedermeyer’s quote by understanding that you are in control of your actions. Your mind is just a powerhouse of both good and evil thoughts.

21 – “The pupil dilates in darkness and in the end finds light, just as the soul dilates in misfortune and in the end finds God.” -Victor Hugo

This quote by Victor Hugo, Les Misérables encourages you to remain positive even during the dark day of your depression.


via 21 Positivity Quotes to Help You Beat Depression – Timeless Life

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[WEB SITE] New MRI scans reveal brain features of depression

Recent advances in brain scanning may bring welcome news to people with depression. Two new types of MRI appear able to spot distinct brain characteristics of the condition.

doctor showing patients a brain scan on a tablet

New MRI scans may reveal previously unknown differences in the brains of people with depression.

The researchers say that their findings deepen knowledge about how depression affects the brain and should lead to better treatments.

One of the new types of MRI reveals differences in the blood-brain barrier (BBB), and the other highlights differences in the brain’s complex network of connections.

Scientists recently used the novel MRI technologies in people with or without major depressive disorder (MDD).

Presentations on the findings are featuring this week at RSNA 2019, the 105th annual meeting of the Radiological Society of North America, which is taking place in Chicago, IL.

According to the World Health Organization (WHO), depression affects more than 264 million peopleTrusted Source worldwide.

Depression and the BBB

Depression is more than the feelings of sadness that most people experience in day-to-day life. It can be a serious health condition, especially when symptoms persist. The most severe forms of depression can lead to suicide.

Loss of interest in daily activities, feelings of hopelessness, and fatigue are some of the main symptoms of MDD.

While scientists know that brain changes accompany the symptoms of MDD, their understanding of the underlying mechanisms is insufficient to meet the urgent need for better treatments.

Kenneth T. Wengler, Ph.D., a researcher in the Department of Psychiatry at Columbia University, in New York, was the first author of the study that examined links between MDD and changes to the BBB.

“Unfortunately,” says Wengler, “with current treatments [for MDD] there is a large chance of relapse or recurrence.”

“To develop new, more effective treatments, we must improve our understanding of the disorder,” he adds.

The BBB is a unique set of properties in the brain’s blood vessels that allow them to control the movement of molecules and cells between them and the tissues that they serve.

The BBB shields the brain from harmful toxins and pathogens that might be in the bloodstream.

Reduced water permeability in the BBB

Wengler and colleagues used a new type of MRI that they had developed themselves. The method, which they named “intrinsic diffusivity encoding of arterial labeled spins,” or IDEALS, allows scientists to investigate the movement of water across the BBB.

They used the new MRI to investigate the BBBs of 14 individuals with MDD and 14 healthy control participants.

Scans of the participants’ brains revealed that those with MDD had reduced water permeability in their BBBs; water moved less readily from their blood vessels into brain tissue than it did in the healthy controls.

The difference in BBB water permeability was particularly marked in two brain regions: the amygdala and the hippocampus. Previous imaging research in people with MDD has also highlighted these two regions.

“We observed disruption of the blood-brain barrier in gray matter regions known to be altered in [MDD],” Wengler explains.

Disruption to the connectome

The second study investigated disruptions to what scientists call the connectomeTrusted Source, or the “complete, point-to-point spatial connectivity of neural pathways in the brain.”

Previous studies that have examined the connectome in relation to MDD have tended to focus on connectivity among brain regions.

The new study is different, in that it takes a deeper look at the connectome within brain regions.

Guoshi Li, Ph.D., a researcher from the Image Display, Enhancement, and Analysis Group at the University of North Carolina School of Medicine, in Chapel Hill, was the first author.

Li and colleagues used functional MRI (fMRI) accompanied by a new tool called a multiscale neural model inversion framework. They used the new method to scan 66 adults with MDD and 66 healthy control participants.

These techniques allowed the team to look at activity in microscopic circuits in relation to large-scale brain activity. They assessed excitation and inhibition among circuits of brain cells. A healthy brain works best when there is a balance between excitation and inhibition.

The fMRI scan results showed that in the dorsal lateral prefrontal cortex, individuals with MDD had different patterns of excitation and inhibition, compared with the individuals who did not have MDD.

The dorsal lateral prefrontal cortex is a region of the brain that helps regulate self-control and emotions. Its function includes the regulation of the amygdala. Scientists have long believed that depressive symptoms can arise when the brain fails to inhibit the amygdala correctly.

“In our study,” says Li, “we found that excitation and inhibition in the brain regions in control of executive functions and emotional regulation were reduced in patients with MDD.”

“This suggests that control functions in MDD are impaired, which may lead to elevated responses in the amygdala, resulting in increased anxiety and other negative moods,” he adds.

The researchers also found that another brain area involved in emotion regulation, the thalamus, tended to show higher recurrent excitation in individuals with MDD.

Li says that the new findings will help scientists fathom the deeper brain connectivity features of depression. He explains that until now, all they had was a “superficial understanding of connectivity.”

This method allows us to identify impaired connectivity within each brain region, making it a potentially more powerful tool to study the neuromechanism of brain disorders and develop more effective diagnosis and treatment.”

Guoshi Li, Ph.D.

The RSNA 2019 program gives the following details about the two studies, which have yet to feature in peer-reviewed journals:

“Blood-Brain Barrier Water Permeability Disruption in Major Depressive Disorder” was presented at session SSM19-05 on Wednesday, December 4th, 2019.

“Multiscale Modeling of Intra-Regional and Inter-Regional Connectivities and Their Alterations in Major Depressive Disorder” was presented at session SSJ19-04 on Tuesday, December 3rd, 2019.


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[TED Talks PLAYLIST] Overcoming depression

Overcoming depression

Depression is an illness that many suffer alone. These speakers bravely share their own stories — and how they recovered.

via Overcoming depression | TED Talks


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[WEB SITE] Traumatic brain injuries could be healed using peptide hydrogels

Traumatic brain injury (TBI) –– defined as a bump, blow or jolt to the head that disrupts normal brain function –– sent 2.5 million people in the U.S. to the emergency room in 2014, according to statistics from the U.S. Centers for Disease Control and Prevention. Today, researchers report a self-assembling peptide hydrogel that, when injected into the brains of rats with TBI, increased blood vessel regrowth and neuronal survival.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

“When we think about traumatic brain injuries, we think of soldiers and athletes,” says Biplab Sarkar, Ph.D., who is presenting the work at the meeting. “But most TBIs actually happen when people fall or are involved in motor vehicle accidents. As the average age of the country continues to rise, the number of fall-related accidents in particular will also increase.”

TBIs encompass two types of injuries. Primary injury results from the initial mechanical damage to neurons and other cells in the brain, as well as blood vessels. Secondary injuries, which can occur seconds after the TBI and last for years, include oxidative stress, inflammation and disruption of the blood-brain barrier. “The secondary injury creates this neurotoxic environment that can lead to long-term cognitive effects,” Sarkar says. For example, TBI survivors can experience impaired motor control and an increased rate of depression, he says. Currently, there is no effective regenerative treatment for TBIs.

Sarkar and Vivek Kumar, Ph.D., the project’s principal investigator, wanted to develop a therapy that could help treat secondary injuries.

We wanted to be able to regrow new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI. Also, we wanted to create an environment where neurons can be supported and even thrive.”

Biplab Sarkar, Ph.D., New Jersey Institute of Technology

The researchers, both at the New Jersey Institute of Technology, had previously developed peptides that can self-assemble into hydrogels when injected into rodents. By incorporating snippets of particular protein sequences into the peptides, the team can give them different functions. For example, Sarkar and Kumar previously developed angiogenic peptide hydrogels that grow new blood vessels when injected under the skin of mice.

To adapt their technology to the brain, Sarkar and Kumar modified the peptide sequences to make the material properties of the hydrogel more closely resemble those of brain tissue, which is softer than most other tissues of the body. They also attached a sequence from a neuroprotective protein called ependymin. The researchers tested the new peptide hydrogel in a rat model of TBI. When injected at the injury site, the peptides self-assembled into a hydrogel that acted as a neuroprotective niche to which neurons could attach.

A week after injecting the hydrogel, the team examined the rats’ brains. They found that in the presence of the hydrogel, survival of the brain cells dramatically improved, resulting in about twice as many neurons at the injury site in treated rats than in control animals with brain injury. In addition, the researchers saw signs of new blood vessel formation. “We saw some indications that the rats in the treated group were more ambulatory than those in the control group, but we need to do more experiments to actually quantify that,” Sarkar says.

According to Kumar, one of the next steps will be to study the behavior of the treated animals to assess their functional recovery from TBI. The researchers are also interested in treating rats with a combination of their previous angiogenic peptide and their new neurogenic version to see if this could enhance recovery. And finally, they plan to find out if the peptide hydrogels work for more diffuse brain injuries, such as concussions. “We’ve seen that we can inject these materials into a defined injury and get good tissue regeneration, but we’re also collaborating with different groups to find out if it could help with the types of injuries we see in soldiers, veterans and even people working at construction sites who experience blast injuries,” Kumar says.

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[Images] 137 Artists Try To Show What Depression Looks Like And Some Results Will Make Your Skin Crawl

Living with depression is hard, but it is treatable, so if you think that you might be suffering from it or spot the first depression symptoms with your relative or a friend, don’t ignore it. Get help.

#1 Brain Sick

Brain Sick

Robert Carter, Final score: 156points

#2 Mind Devour

Mind Devour

The painting describes a person with psychological problems such as schizophrenia, insanity, depression or other mental problems. His endless screaming makes his own mind eat him up. I have periods in my life where I feel like this. I wanted to make an illustration of my thoughts and my pain within.

Sebmaestro, Final score:148points

MORE —-> 137 Artists Try To Show What Depression Looks Like And Some Results Will Make Your Skin Crawl | Bored Panda

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