Five Major Mental Disorders Share Genetic Roots

March 1, 2013 • Science Update

Five major mental disorders share some of the same genetic risk factors, the largest genome-wide study of its kind has found. Evidence for such genetic overlap had previously been limited to pairs of disorders.

National Institutes of Health-funded researchers discovered that people with disorders traditionally thought to be distinct – autism, ADHD, bipolar disorder, major depression and schizophrenia – were more likely to have suspect genetic variation at the same four chromosomal sites. These included risk versions of two genes that regulate the flow of calcium into cells.

Jordan Smoller, M.D.

Source: Jordan Smoller, M.D., Massachusetts General Hospital

“These results will help us move toward diagnostic classification informed by disease cause,” said Jordan Smoller, M.D. , of Massachusetts General Hospital, Boston, a coordinator of the study, which was supported by NIH’s National Institute of Mental Health. “Although statistically significant, each of these genetic associations individually can account for only a small amount of risk for mental illness, making them insufficient for predictive or diagnostic usefulness by themselves.”

Smoller, Kenneth Kendler, M.D., , Virginia Commonwealth University, Richmond; Nicholas Craddock, PhD. , Cardiff University, England;Stephan Ripke, M.D. , Massachusetts General, Patrick Sullivan, M.D. , University of North Carolina at Chapel Hill, and colleagues in the Cross-Disorder Group of the Psychiatric Genomics Consortium, report on their findings February 28, 2013 in The Lancet.

Prior to the study, researchers had turned up evidence of shared genetic risk factors for pairs of disorders, such as schizophenia and bipolar disorder, autism and schizophrenia and depression and bipolar disorder. Such evidence of overlap at the genetic level has blurred the boundaries of traditional diagnostic categories and given rise to research domain criteria, or RDoC, an NIMH initiative to develop new ways of classifying psychopathology for research based on neuroscience and genetics as well as observed behavior.

To learn more, the consortium researchers analyzed the five key disorders as if they were the same illness. They screened for evidence of illness-associated genetic variation across the genomes of 33,332 patients with all five disorders and 27,888 controls, drawing on samples from previous consortium mega-analyses.

For the first time, specific variations significantly associated with all five disorders were among several suspect genomic sites that turned up. These included variation in two genes that code for the cellular machinery for regulating the flow of calcium into neurons. Variation in one of these, called CACNA1C, which had previously been implicated in susceptibility to bipolar disorder, schizophrenia and major depression, is known to impact brain circuitry involved in emotion, thinking, attention and memory – functions disrupted in mental illnesses. Variation in another calcium channel gene, called CACNB2, was also linked to the disorders.

Alterations in calcium-channel signaling could represent a fundamental mechanism contributing to a broad vulnerability to psychopathology, suggest the researchers.

They also discovered illness-linked variation for all five disorders in certain regions of chromosomes 3 and 10. Each of these sites spans several genes, and the specific causal factors within them remain elusive. However, one region, called 3p21, which produced the strongest signal of illness association, harbors suspect variations identified in previous genome-wide studies of bipolar disorder and schizophrenia.

References

Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. The Lancet, February 28, 2013

Grant # 1  U01  MH085520  01 

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Symptoms Outdo Diagnoses in Predicting Bipolar Disorder in At-Risk Youth February 26, 2016 • Science Update

Three types of symptoms emerged as powerful predictors of whether a youth with one parent with bipolar disorder will go on to develop the disorder, according to a study of 391 at-risk youth. The findings offer a much more specific roadmap than previously available for assessing risk of bipolar disorder early in at-risk youth, and one that is based on symptoms, not traditional psychiatric diagnoses. The symptoms identified—related to anxiety/depression, affective lability (unstable mood, including irritability), and low-level manic symptoms—also provide insight into what may be a high-risk syndrome or “prodrome” preceding the onset of bipolar spectrum disorder.

People with bipolar disorder experience marked, often extreme shifts in mood and energy. The disorder affects an estimated 2.6 percent of Americans. Someone with bipolar disorder experiences periods of depression alternating with periods of mania, a state marked by high energy, overconfidence, and frantic activity. The mood swings can severely disrupt a person’s ability to function normally; as many as 15 percent of those affected die by suicide. Despite this, there are often years-long delays before an accurate diagnosis and appropriate treatment. Research has suggested that a bipolar prodrome might precede the emergence of bipolar disorder by several years; the hope is that identifying the features of the prodrome could help guide an understanding of how the disorder emerges, and enable earlier detection and more timely and effective treatment.

Scientists participating in the NIMH-funded Pittsburgh Bipolar Offspring Study (BIOS) recruited children of parents with bipolar disorder and a similar group of 248 youth with no family history of the condition. The BIOS team, at the University of Pittsburgh, followed both groups for an average of eight years, collecting information on symptoms of psychiatric disorders, including depression, anxiety, and attention-deficit hyperactivity disorder. While previous research had found that most people diagnosed with bipolar disorder recalled having symptoms of psychiatric disorders earlier, in order to determine accurately how preexisting symptoms affect risk for later development of a disorder, it’s necessary to study populations prospectively, or over time, starting years before a disorder emerges. This study looked at a relatively large at-risk population; by the end of the study 44 of the participant youth were diagnosed with bipolar disorder.

Previously, the study had reported  on categorical predictors of bipolar disorder—the presence or absence of a collection of symptoms on which a diagnosis is based—such as depression and subthreshold manic episodes. Among their findings was that, taking into account only results based on following youth over time, and not recall of past symptoms, only a previous episode of “subthreshold mania or hypomania”—defined on the basis of symptoms, functioning, and duration—predicted later development of bipolar disorder.

This more recently reported phase of the study, led by Danella M. Hafeman, M.D., Ph.D., and Boris Birmaher, M.D., took a different approach. This study looked at symptoms in different dimensions of function, without reference to umbrella diagnostic categories, and how these symptoms predicted bipolar spectrum disorder.

Levels of several different dimensional symptoms were higher in the high-risk youth when they were first evaluated, including those related to anxiety/depression, inattention/disinhibition, externalizing (disruptive and impulsive behavior), affective lability (unstable mood, including irritability), and low-level manic symptoms (not necessarily part of an episode). Symptom levels in three areas emerged as the strongest predictors of later bipolar disorder: anxiety/depression at baseline (as participants entered the study); affective lability, both at baseline and shortly before a bipolar diagnosis; and low-level manic symptoms shortly before diagnosis. Earlier age at which at which a parent was diagnosed with a mood disorder also increased risk. Youth with all four of those risk factors had a 49 percent chance of developing bipolar, vs. a 2 percent chance for those without them.

At the same time, it’s important to note that over half of those with all four of the most powerful risk factors did not develop bipolar disorder by the end of the study.

The risk factors identified in this study predicted the onset of bipolar disorder whether or not a young person also had a preexisting categorical diagnosis other than bipolar disorder. In fact, the report points out, once the dimensional risk factors were accounted for, disorders no longer predicted future bipolar disorder.

These findings offer an approach to assessing risk on the basis of symptoms without respect to diagnoses. These insights can inform clinical diagnosis, but also provides clues for researchers on the facets of the prodrome. Research suggests that changes are occurring in the brain well before psychiatric disorders like bipolar disorder and schizophrenia emerge with obvious symptoms. Information on this prodromal period can not only make early treatment possible, but could help scientists understand the origin of the brain changes with the aim of eventually being able to interrupt the process and prevent disease.

“This study is the first large effort to document the relevant prodromal factors for bipolar disorder in the context of an unfolding process across time,” said Shelli Avenevoli, Ph.D., acting NIMH deputy director. “It demonstrates the potential of combining dimensional symptoms and family risk to enhance risk prediction and for investigating the nature of the prodrome.”

Lead author Danella Hafeman, M.D., Ph.D., said, “The results of this study begin to define an ultra-high risk population, similar to the work that has been done in psychosis. The identification of such a population is important to clinical practice, identifying patients who might require increased surveillance, as well as future research to evaluate strategies for early intervention.”

Reference

Hafeman DM, Merranko J, Axelson D, Goldstein BI, Goldstein T, Monk K, Hickey MB, Sakolsky D, Diler R, Ivengar S, Brent D, Kupfer D, Birmaher B. Toward the Definition of a Bipolar Prodrome: Dimensional Predictors of Bipolar Spectrum Disorders in At-Risk Youths.  Am J Psychiatry. 2016 Feb 19:appiajp201515040414. [Epub ahead of print]

Grant: MH060952

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What I’m grateful for work sheet

I’m grateful for my family because

 

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Something good that happened this week

 

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I am grateful for my friendship with

 

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I am grateful for who I am because

 

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Something silly that I am grateful for

 

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Something else that I am grateful for

 

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OCD Exposure Hierarchy Packet work sheet

Research supports exposure and response prevention therapy as the leading form of psychotherapy for OCD. As a part of this treatment, your clients will be gradually exposed to their triggers, which results in their anxieties, obsessions, and compulsions diminishing.

This OCD worksheet packet includes a blank exposure hierarchy template, and an exposure therapy homework form. The homework form provides a professional way for you to record your client’s weekly exposure homework, and it gives your clients a nice place to keep track of their progress.

OCD Treatment Overview
Overview of Obsessive-Compulsive Disorder
Diagnostic Criteria of OCD
How Does OCD Work?
Exposure and Response Prevention Therapy
Psychoeducation
OCD Exposure Hierarchy
Exposure and Response Prevention
Handling Mental Compulsions
Other OCD Resources
References

OCD Treatment Overview “I’m so OCD!”

Obsessive-compulsive disorder may be the most popular disorder to say you have, without actually having. In common parlance, “OCD” is used to refer to someone who likes things a particular way, or who seems overly concerned with cleanliness.

In the world of mental health, obsessive-compulsive disorder refers to something more serious. OCD can be scary or frustrating, and by definition, it is time-consuming or impairing.

Overview of Obsessive-Compulsive Disorder

OCD includes two major types of symptoms: obsessions and compulsions. A person diagnosed with OCD can experience both sets of symptoms, or only one of the two.

Obsessions are thoughts, urges, or images that just won’t leave a person alone. They’re perceived as being intrusive and unwanted, and they often lead to feelings of anxiety, shame, and doubt. Some common obsessions include:

Fear of contamination by coming in contact with germs, dirt, or bodily fluids
Unwanted sexual or violent thoughts
Fear of losing control of one’s own actions and acting on negative impulses
Excessive concern about evenness or exactness
Concern about morality or offending God
Fear of causing harm to self or others

Compulsions are repetitive behaviors that a person performs according to a rigid set of rules, or in response to an obsession. Compulsions are intended to reduce anxiety, although they have no realistic connection to the anxiety-producing situation, or they are excessive. Some common compulsions include:

Cleaning or washing excessively
Mentally reassuring oneself that everything is OK
Repeating activities a specific number of times
Rearranging items until they feel just right
Mentally reviewing a situation again and again
Excessively checking that a mistake was not made

Diagnostic Criteria of OCD
To meet the criteria for OCD, the individual must have obsessions or compulsions, or both.

Obsessions
1. Recurrent and persistent thoughts, urges, or impulses, that are experienced at some time during the disturbance as intrusive and unwanted, and often cause anxiety.

2. The individual attempts to ignore or suppress these thoughts, urges, or images, or to neutralize them with another thought or action.

Compulsions
1. Repetitive behaviors or mental acts that an individual feels driven to perform in response to their obsessions or in accordance with a rigid set of rules. These can include hand-washing, checking (such as repeatedly checking that a door is locked), counting, or repeating words silently.

2. The behaviors are intended to reduce anxiety, distress, or some dreaded event. However, the compulsive behaviors are not realistically connected to what the are trying to prevent, or they are excessive.

A diagnosis of obsessive-compulsive disorder also requires that the obsessions and compulsions are time-consuming (for example, they require over 1 hour every day), distressing for the individual, or they cause impairment in an important area of functioning.

Finally, the symptoms of OCD cannot be better explained by another cause, such as a drug or medical condition (including other mental disorders).

Adapted from the DSM-5 by the American Psychiatric Association

How Does OCD Work?
So, how does OCD actually work? First, to understand OCD, you need to know a little bit about anxiety. Your body uses anxiety as an alarm system to warn you about possible dangers. At a low level of perceived danger, your body might experience stress. At a high level of perceived danger, your body will experience fear. Normally, anxiety helps to keep us alive. It stops us from driving far too fast, and it keeps us alert when we walk down a dark street alone.

With OCD, the anxiety alarm system is triggered far too easily, and its warnings are much more intense than necessary. Minor dangers—or dangers that don’t even exist—might trigger a strong anxiety response.

Imagine that someone with OCD touches a doorknob, and becomes overwhelmed with the fear that their hand will become infected (this is the obsession). They immediately wash their hands, but not for 15 seconds like many people might. Instead, they wash their hands for 10 minutes (this is the compulsion).

The brain takes note of the serious response to touching a doorknob, and confirms to itself that touching doorknobs must be dangerous. Furthermore, the brain notices that the anxiety did in fact diminish after 10 minutes of hand washing, so it must have helped. This creates a negative feedback loop where small sources of anxiety result in extreme responses, which then further reinforce the obsessions and compulsions.

Diagram depicting the cycle of OCD.

During the treatment of OCD, this cycle will be identified and broken. One form of treatment that focuses on the disruption of this cycle is called exposure and response prevention therapy.

Exposure and Response Prevention Therapy

Exposure and response prevention therapy (ERP) is a form of psychotherapy that’s well supported, and commonly used, for the treatment of OCD. It falls under the broader category of cognitive behavioral therapy, and you may notice several similarities to the treatment of anxiety disorders.

Some forms of psychotherapy, such as those based around insight and finding the root cause of problems, may do more harm than good when it comes to OCD. They simply place more focus upon obsessions and compulsions, without providing any tools to manage them.

In the course of ERP, the client will be exposed to the sources of their anxiety, obsessions, and compulsions. As the client is exposed to their triggers, they will practice refraining from their compulsive behaviors. This will break the cycle of avoidance and the reinforcement of anxiety.

Psychoeducation
Before moving into the exposure portion of treatment, clients should have an understanding of how OCD works, what their obsessions and compulsions are (and how they are harmful), and how exposure will help them. Exposure therapies are, by definition, uncomfortable for clients. Few will consider facing their fears unless they believe in the treatment.

Proper psychoeduation includes a discussion about the length of treatment. Don’t expect a significant change in obsessions and compulsions after only one week. Explain that, at first, your client will simply be resisting their compulsions. It won’t feel great. After a week or more of practice, their anxiety will slowly begin to diminish. And then, in time, their obsessions and compulsions will also begin to fade (which will further reduce the anxiety).

OCD Exposure Hierarchy
Before beginning exposure, you’ll need to identify specific obsessions, compulsions, and sources of anxiety that you would like to target. This will require some exploration and analysis. Give special attention to situations that your client tends to avoid due to their anxiety.

This portion of treatment can also include discussion regarding the meaning of compulsions and rituals to your client. It can be valuable to begin labeling obsessions and compulsions as such.

After exploring your client’s sources of anxiety, collaborate to record them on an OCD Exposure Hierarchy form. Each trigger should be ranked and listed from the most to least distressing.

Worksheet IconOCD Exposure Hierarchy
worksheet

Example OCD Exposure Hierarchy Work sheet
Anxiety Obsession Compulsion

Trigger______________________________________________________________________________________________________________.

Level of Distress_________________________________________________________________________________________________________.

(1-10)
Using a public restroom. 9
Shaking a stranger’s hand. 7
Handling money. 5
Touching a doorknob in a public place. 2

The exposure hierarchy lays out a roadmap for the rest of treatment. Clients will face their triggers beginning with the least distressing items, and moving to more difficult levels as they improve. For this reason, be sure to list a variety of triggers, including some that that only cause a low level of distress, with a steady progression toward greater levels of distress.

Exposure and Response Prevention
During the exposure stage of treatment, your client will face a distressing situation (beginning at the bottom of the exposure hierarchy) and consciously refrain from their compulsion for at least two hours. This task should be practiced daily. Exposure can begin in session, but it should also continue throughout the week as homework. The standard hour-a-week sessions simply don’t leave enough time for adequate exposure.

Based upon the example exposure hierarchy from above, the client will first be asked to touch a doorknob in a public place, and then refrain from their compulsion (e.g. washing their hands) for two hours. During this time they will most likely experience anxiety and the desire to act on their compulsion, but they will consciously refrain.

If your client can’t contain their compulsions after grabbing a doorknob, ask them to touch it with only one finger. Be creative to come up with forms of exposure that are challenging, but not impossible.

As a normal, empathy-feeling human, you may be tempted to reassure your client that “everything will be OK” during exposure. While it’s fine to explain at the beginning of treatment that your client will never be placed in danger during their sessions, reassurance during exposure acts as a form of avoidance. Remember, your client is supposed to be experiencing anxiety, and reassuring them contradicts that goal.

Tip: In extreme cases where even the smallest trigger is too much for your client, collaborate to create a narrative about exposure to the trigger. In this narrative, your client’s fears should be realized. Remember, the goal is to incite anxiety, not to tell a fun story where everything goes great! Ask your client to vividly imagine the narrative.

One important note: Imagination is not a replacement for real life exposure. It’s just one step toward the next stage of the hierarchy.

After your client has become more comfortable with the lowest level of the hierarchy, move to the next trigger on the list. The anxiety associated with each level doesn’t have to totally disappear before you move on, but the next task should feel manageable (although challenging).

As a basic model for the progression through this stage of treatment, try to introduce your client to a new level on the exposure hierarchy each week during their therapy session. If possible, begin practicing the exposure in session, and ask that your client also practices every day at home until they return for their next session. The importance of properly completing the homework cannot be emphasized enough. Ask your client to set a timer for two to three hours after exposure to their trigger to keep track of how long they must resist their compulsion. No cheating!

Of course, the time frame for treatment will differ case-by-case. Use your professional judgement to move your client through the hierarchy at a pace that’s appropriate for them.

Tip: It is a common mistake to end treatment before a client has addressed their biggest fears. Treatment should address the full exposure hierarchy, and not stop early because it seems “close enough”. Unaddressed triggers can grow, and the anxiety will spread back to areas that were previously under control.

Handling Mental Compulsions
Mental compulsions, such as self-reassurance, internal counting, special prayers, mentally reviewing situations, and others, can pose a special challenge during response prevention. Mental compulsions are often automatic and almost involuntary.

Oftentimes, therapists’ natural response to this challenge is to teach clients to distract themselves. This may treat the symptoms in the moment, but not the underlying issue. Distraction works as a form of avoidance from the anxiety.

Instead, clients should be taught to “spoil” their mental compulsions by re-exposing themselves to the trigger with their thoughts.

For example, someone might experience a great deal of anxiety after having normal conversations. Afterwards, they mentally review the conversation again and again, looking for evidence that they acted normally. This mental process can be spoiled by replacing the reassuring thoughts with alternatives such as: “I might have made a fool of myself during that conversations.”

Spoiling the reassuring thoughts forces the client to continue their exposure to the anxiety, which will eventually result in its diminishment.

Other OCD Resources
We’ve collected several resources related to OCD to help you continue your education:

Book IconERP for OCD: Therapist Guide
book

Book IconA Kid’s Guide to Overcoming OCD
book

References
Abramowitz, J. S. (1996). Variants of exposure and response prevention in the treatment of obsessive-compulsive disorder: A meta-analysis. Behavior therapy, 27(4), 583-600.

Gillihan, S. J., Williams, M. T., Malcoun, E., Yadin, E., & Foa, E. B. (2012). Common pitfalls in exposure and response prevention (EX/RP) for OCD. Journal of obsessive-compulsive and related disorders, 1(4), 251-257.

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Thought Log

EVENT____________________________________________________________

 

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CONSEQUENCE / BEHAVIOR

 

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RATIONAL COUNTER STATEMENT

 

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