Are Epilepsy And Bipolar Disorder Related

Ion Channels As Therapeutic Targets

Ion channels provide an attractive target for pharmacological intervention, given their diverse and ubiquitous roles in a broad range of physiological processes. Among all drugs with known targets, approximately 13.4% have their primary therapeutic action at ion channels. This ranks ion channels second as a target class, behind G protein-coupled receptors .

Voltage-gated potassium channels, specifically the Kv7 channels, are particularly attractive targets for novel therapeutics for BP. In addition to their functionally relevant roles within neurons, they offer the ability for selective intervention . For example, ezogabine is a neuronal potassium channel enhancer that was recently approved by the FDA to treat partial epilepsy . It has been shown that EZG activates the KCNQ2/KCNQ3 hetero-tetramer ion channel complex, which in turn promotes the M-current and thereby stabilizes action potential firing. This action likely accounts for the drugs anticonvulsant properties .

Ezogabine has also been evaluated for the acute treatment for mania in a small open label pilot study of treatment resistant in patients with BP type I . Despite the limited sample, the brevity of the study design, and the severity of illness, improvement in mania scores was observed in four patients. The treatment was well tolerated with no depressogenic effects, indicating that further study may be warranted.

Symptoms Of Anxiety In Epilepsy

Symptoms of anxiety in epilepsy may result or be exacerbated by psychological reactions, including responses to the unpredictability of seizures and restrictions of normal activities. This results in low self-esteem, stigmatization, and social rejection. According to Goldstein and Harden, epileptic events can produce symptoms indistinguishable from those of primary anxiety disorder.

Fear and anxiety are often associated with simple partial seizures. Torta and Keller estimated that fear occurs as an aura in as many as 15% of patients, and Goldstein and Harden concluded from several studies that fear is one of the most common ictal emotions.

Ictal anxiety symptoms manifest as fear or panic, sometimes with other characteristics of temporal discharges, such as depersonalization and déjà vu, as well as other psychological and autonomous phenomena.

Psychiatric Symptoms May Be Caused By Epilepsy

Epileptic seizures can resemble psychiatric disorders. Prolonged epileptic seizures such as in complex partial status epilepticus can give rise to long-term impaired consciousness, automatisms, affective changes, confusion, amnesia, fear or schizophreniform disorder symptoms . Temporal lobe epilepsy can cause sudden, temporary anxiety or deep despair . Frontal lobe epilepsy can manifest itself in seizures with bizarre behaviour. Important differential diagnoses are, among others, panic disorder, parasomnia and psychogenic seizures.

Depressive or psychotic episodes can also be time-related to an epilepsy seizure. Many patients with epilepsy report prodromal mood changes 13 days prior to a seizure. Epileptic seizures can also be followed by temporary psychiatric symptoms, such as postictal psychosis or postictal depression. There is typically a symptom-free interval of up to one week .

Since, as we have seen, it can be difficult to distinguish between epilepsy and psychiatric disorders, patients with acute psychiatric symptoms should generally be examined by both a psychiatrist and a neurologist, and an EEG test should be performed whether the patient has known epilepsy or not.

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Psychiatric Disorders After Epilepsy Diagnosis: A Population

• Affiliation School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan

• Affiliations Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan, Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan

• Affiliations Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan, College of Medicine, Taipei Medical University, Taipei, Taiwan

• Affiliation Department of Psychiatry, Wan Fang Medical Center, affiliated with Department of Psychiatry, College of Medicine, Taipei Medical University, Taipei, Taiwan

• * E-mail:

  Affiliations Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan, Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan

Treatment For Depression And Anxiety

• Medications
• Typically a class of medications known as selective serotonin reuptake inhibitors are used to treat depression and/or anxiety.
• Some anti-seizure medications are also associated with improved mood, including Neurontin, Lamictal, Topamax, Depakote

What is Cognitive Behavioral Therapy?

CBT treatment usually involves efforts to change thinking patterns. These strategies might include:

• Learning to recognize ones distortions in thinking that are creating problems, and then to reevaluate them in light of reality.
• Gaining a better understanding of the behavior and motivation of others.
• Using problem-solving skills to cope with difficult situations.
• Learning to develop a greater sense of confidence is ones own abilities.
• CBT is a collaborative approach between the patient and therapist. This is not a lay on the couch style of therapy! The therapist will be more directive, almost acting as a coach, rather than a passive listener.

CBT can be highly effective in as little as 8-12 visits.

What is Mindfulness?

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How Are Seizures Related To My Disorder

In general, we use the word seizures to describe what people experiencesudden spells when someone loses awareness or becomes disoriented. We use the term epilepsy to describe an electrical pattern in the brainusually diagnosed by an electroencephalogram or EEG. Not all seizures are due to epilepsy, and not all electrical epilepsy in the brain results in a seizure.

People with mood disorders are more likely to experience seizures of both kindsseizures that are due to epilepsy and seizures that are not. And it seems that the relationship flows in both directions: having a mood disorder increases the risk of seizures, and having seizures increases the risk of a mood disorder. We understand only a little about the specifics of those relationships. For example, epilepsy in the temporal lobe of the brain may be more strongly linked to mood disorder or mood changes. Youre certainly right that the brain is a complex thing!

Some of the medications used to treat bipolar disorder, like lamotrigine or valproate, were originally developed to treat epileptic seizures. That is more evidence of the relationship between mood disorders and seizures. But, again, it is complex: not all anticonvulsant medications are effective for the treatment of mood disorders.

About the Doc

About the Doc

A Review Of Potassium Channels In Bipolar Disorder

• 1Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA
• 2Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

Although bipolar disorder is one of the most heritable psychiatric conditions, susceptibility genes for the disorder have yet to be conclusively identified. It is likely that variants in multiple genes across multiple pathways contribute to the genotypephenotype relationship in the affected population. Recent evidence from genome-wide association studies implicates an entire class of genes related to the structure and regulation of ion channels, suggesting that the etiology of BP may arise from channelopathies. In this review, we examine the evidence for this hypothesis, with a focus on the potential role of voltage-gated potassium channels. We consider evidence from genetic and expression studies, and discuss the potential underlying biology. We consider animal models and treatment implications of the involvement of potassium ion channelopathy in BP. Finally, we explore intriguing parallels between BP and epilepsy, the signature channelopathy of the central nervous system.

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Public Enemy No : Depression And Mood Disorders In People With Epilepsy

A link between mood disorders and epilepsy has been noted for more than 2,000 years. While we understand this association more today than in the past, much work needs to be done to more clearly clarify whether this is a causative association.

What is relatively clear, however, is the fact that depression adversely affects the quality of life of people with epilepsy, and it needs to be recognized and treated when appropriate. This article will cover definitions of mood disorders in people with epilepsy, as well as their incidence, recognition, causes and treatment options.

What are Mood Disorders?

To put it simply, mood disorders are conditions that negatively affect an individuals emotional state. For people with epilepsy, the most common mood disorders are major depression and dysthymia.

Sadness, albeit a common occurrence in our daily lives, is a primary symptom of depression. Yet, persistent and excessive sadness is considered abnormal and open to treatment.

There are a host of symptoms that point to treatable depression: sadness associated with a lack of pleasure in performing activities problems with weight and sleep tiredness difficulty concentrating and making decisions feelings of worthlessness or guilt and frequent thoughts of suicide and death. If five or more of these symptoms persist for at least two weeks, that qualifies as major depressive disorder.

Recognition and Incidence of Mood Disorders

Eeg And Quantitative Eeg

The EEG signal is composed of synchronised synaptic potentials in the cerebral cortex and appears as wave forms made up of different frequencies and rhythms. In the EEG of healthy adults and adults in a waking state, the activity consists mainly of alpha waves in the 813 Hz frequency range and some beta waves in the 1430 Hz frequency range, while there are few theta waves in the 47 Hz frequency range and almost no visible delta waves in the 0.53 Hz frequency range. Table 1 shows in which neural networks the different frequencies can be found . During drowsiness and sleep, an EEG will show more slow waves. Drugs that affect the brain can also change the speed of the EEG rhythms.

Table 1

¹ Also involved in synchronisation between brain regions

Epileptiform activity consists of sharp waves or a «spike-and-wave» pattern. This is a specific sign of epilepsy if the patient also has seizure symptoms which can fit the diagnosis. The probability of finding epileptiform activity in a patient with epilepsy increases if the EEG is recorded while the patient is sleeping .

Fig. 1

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What If I Take Too Much

Taking too much lamotrigine can cause serious side effects.

Immediate action required: Call 999 or go to A& E if:

You take too much lamotrigine and:

• have rapid, uncontrollable eye movements
• feel clumsy or lose your balance
• feel a change in the rhythm of your heartbeat
• have had a fit or seizure
• pass out

Do not drive yourself. Get someone else to drive you or call for an ambulance.

If you need to go to hospital, take the lamotrigine packet or the leaflet inside it, plus any remaining medicine, with you.

Why Is It So Rare

Mania in epilepsy is rare, with the exception of two specific conditions: postictal psychosis and mania after epilepsy surgery.

Kanemoto studied systematically the differences between 126 patients with interictal and 46 patients with postictal psychoses. With respect to psychopathology , he identified two distinct patterns. He noticed that mania-related symptoms such as logorrhea and delusions of grandiosity are much more common in postictal psychosis as compared with interictal psychosis, characterized by schizophreniform delusions and hallucinations. He also noted a predominance of patients with temporal lobe epilepsies in both psychosis groups however, this link was even more striking in patients with postictal psychosis, of whom 87% were diagnosed with temporal lobe epilepsy, 82% had complex partial seizures, and 35% had structural abnormalities of the temporal lobe on magnetic resonance imaging . The corresponding data for patients with interictal psychosis were 59% for temporal lobe epilepsy, 67% had complex partial seizures, and 20% displayed temporal lobe MRI abnormalities .

Figure 1

Postictal versus interctal psychoses . Psychopathology. PiP: n = 45 IiP: n = 126.

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Evidence Of Familial Vulnerability For Epilepsy And Psychosis

Date:

Elsevier

Summary:

Although the two disorders may seem dissimilar, epilepsy and psychosis are associated. Individuals with epilepsy are more likely to have schizophrenia, and a family history of epilepsy is a risk factor for psychosis. It is not known whether the converse is true, i.e., whether a family history of psychosis is a risk factor for epilepsy.

Although the two disorders may seem dissimilar, epilepsy and psychosis are associated. Individuals with epilepsy are more likely to have schizophrenia, and a family history of epilepsy is a risk factor for psychosis. It is not known whether the converse is true, i.e., whether a family history of psychosis is a risk factor for epilepsy.

Multiple studies using varied investigative techniques have shown that patients with schizophrenia and patients with epilepsy show some similar structural brain and genetic abnormalities, suggesting they may share a common etiology.

To investigate this possibility, researchers conducted a population-based study of parents and their children born in Helsinki, Finland. Using data available in two Finnish national registers, the study included 9,653 families and 23,404 offspring.

Individuals with epilepsy had a 5.5-fold increase in the risk of having a psychotic disorder, a 6.3-fold increase in the risk of having bipolar disorder, and an 8.5-fold increase in the risk of having schizophrenia.

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Consequences For Treatment Of Epileptiform Eeg Activity

If epileptiform activity is found in an EEG, a neurologist should assess whether there is clinical epilepsy or not. Psychiatric disorders and symptoms caused by current epileptic activity should be treated with antiepileptic drugs. Treatment with such drugs may be necessary in exceptional cases even if an EEG does not show epileptiform activity, because ictal and postictal psychosis can be caused by deep-lying limbic epileptiform activity . Treatment with antiepileptic drugs may, however, be indicated for some non-epileptic patients, although a Cochrane Review has recommended that carbamazepine should not be used routinely to treat schizophrenia . Pathological EEG findings will increase the indication for administering antiepileptic drugs compared with other psychotropic drugs, irrespective of the psychiatric core symptoms .

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Is Eeg A Useful Test In Adult Psychiatry

Trond Sand Specialist in clinical neurophysiology and neurology. He is a senior consultant at the Section for neurophysiology and professor of clinical neurophysiology.

The author has completed the ICMJE form and declares no conflicts of interest.

PhD in neuroscience and experience of clinical research using EEG. She is a medical doctor specialising in neurology and a post-doctoral research fellow in epilepsy.

The author has completed the ICMJE form and declares the following conflicts of interest: She was awarded the Pfizer Neuroscience Prize in 2010 and has received a travel grant from GlaxoSmithKline.

Haukeland University Hospital

Arne E. Vaaler Specialist in psychiatry. He is a senior consultant and senior lecturer.

The author has completed the ICMJE form and declares no conflicts of interest.

Østmarka Psychiatric Department

Norwegian University of Science and Technology

Is There An Epilepsy

The clinical diagnosis of depression in epilepsy can be very difficult. First, most patients do not complain about mood problems. Depressive epilepsy patients often describe symptoms that may easily be interpreted as a side effect of antiepileptic drugs or as a consequence of epilepsy per se. Such misleading complaints may relate to sleep problems, changes in appetite, loss of libido, and impairment of cognition. A frequent complaint of depressed epilepsy patients relates to poor memory. An English study demonstrated that patients who complain about memory problems are significantly more depressed and anxious than are noncomplainers . Elixhauser et al. performed neuropsychological assessments in depressed and nondepressed epilepsy patients who described memory problems. In patients with depression, subjective memory impairment was not related to objective memory performance. These findings highlight the importance of psychiatric assessments to detect depressive syndromes .

Diagnostic criteria for a depressive syndrome according to ICD-10, DSM-IV

• aKnown side effects of anticonvulsants.

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Can Epilepsy Be Related To Bipolar

Well, it’s official…I’ve been diagnosed with temporal lobe epilepsy. So far, I’ve only had simple partial seizures. I get this strong deju vu and detached feeling, I can hear everything going on around me, and can move normally, but can only speak single words. These seizures last for maybe 20 or 30 seconds, then I feel ‘normal’. The doctor wants to put me on Depakote. My GP says she thinks I’m bipolar, and that Depakote would be a treatment for that also. I get these mood swings, from depression to anger to numbness, sometimes all within the course of one day.

I’ve researched this online, and have found some studies that suggest that bipolar and epilepsy could be related conditions, and that bipolar could even actually be a form of epilepsy. Has anyone else had similar experiences or found any similar information to share?

Thanks

Genetic Findings With Potassium Ion Channels

Because of the findings with CACNA1C, most of the attention has understandably focused on the role of calcium ion channels in BP. However, the possibility that potassium ion channels may also contribute to the etiology of BP was suggested by a re-analysis of GWAS data from the NIMH GAIN sample . Given that ANK3 encodes a protein known to molecularly interact with other membrane bound proteins in neurons, we sought to test whether interactions between ANK3 and genes encoding these other proteins may contribute to BP susceptibility. Using the STRING 9.0 bioinformatics database , which collates existing evidence of proteinprotein interactions, we identified putative interactors with ANK3. We then tested for interactions between SNPs in ANK3 and in these interacting proteins in association with BP. The most significant findings were between ANK3 and KCNQ2 , which remained significant after accounting for multiple testing. These interactions were driven by two SNPs in KCNQ2, rs2282150 and rs2297385 , interacting with 16 different SNPs in ANK3 that all fall within the boundaries of ankyrin repeats, which are functional domains known to mediate proteinprotein interactions. We were able to replicate these associations using data from the WTCCC sample. We also found suggestive evidence of interactions between ANK3 and KCNQ3 . KCNQ2 and KCNQ3 encode proteins that form hetero-tetramer complexes making up the voltage-gated potassium ion channels in neurons.

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