Thursday, August 12, 2010

Short Description of Obsessive-Compulsive Disorder (OCD)

 Retrieved From:
Stanford Med. School

Obsessive-compulsive disorder (OCD) was described as early as the seventeenth century, when the Oxford Don, Robert Burton, reported a case in his compendium, The Anatomy of Melancholy (1621). Modern concepts of OCD began to evolve in France and Germany in the nineteenth century. In the late twentieth century we have begun to understand the biology of this mental disorder, as neurochemical assay and brain imaging techniques have become available.

Age at Onset 


OCD usually begins before age 25 years and often in childhood or adolescence. In individuals seeking treatment, the mean age of onset appears to be somewhat earlier in men than women. According to Swedo et al.'s report in 1989, in a series of 70 children and adolescents seen at the National Institute of Mental Health, the mean age of onset was 9.6 years for boys and 11.0 for girls. In a series of 263 adult and child patients, Lensi et al. in 1996 reported that the mean age at onset was 21 years for men and 24 years for women. Still, in another series reported by Rasmussen and Eisen in 1992, the means were 21 years for men and 22 years for women -- in this series, major symptoms began before age 15 years in about one-third, before age 25 in about two-thirds, and after age 35 in less than 15%.

In one series of 200 patients reported by Rasmussen and Eisen in 1988, 29% felt that an environmental precipitant had triggered their illness, most frequently increased responsibility, such as the birth of a child, or significant losses, such as a death in the family, while Williams and Koran reported in 1997 that of 100 women in their study, 62% reported premenstrual worsening.

In community surveys, the results are mixed. The Epidemiological Catchment Area survey (ECA), which utilized lay interviewers (trained non-professionals) to examine more than 18,500 individuals in five cities reported a similar mean age of onset for men and women identified as OCD cases (22.4 and 23.0 years). A similar study in Edmonton, Canada reported a slightly later median age of onset for males (age 20 years) than females (age 19 years). Among 56 individuals in their mid-20s with obsessive-compulsive syndrome identified in a Zurich survey, the mean age of onset was 17 years for males and 19 years for females.

Course and Prognosis


For most adult patients who come to treatment, OCD appears to be a chronic condition. In their series of 560 patients in 1988, Rasmussen and Eisen reported that 85% had a continuous course with waxing and waning symptoms, 10% a deteriorative course and only 2% an episodic course marked by full remissions lasting six months or more. An Italian series by Lensi et al. in 1996 reported more patients with episodic or deteriorative courses in which 26% were episodic, 9% were deteriorative, and 64% were chronic. The conclusions drawn from studies that predate current diagnostic criteria, effective treatments and current patterns of health care utilization should not be applied to today's patients.

The prognosis of children and adolescents who present for treatment appears to be good for half or more. Leonard et al. reported in 1993, that a little more than half of 54 children and adolescents were only mildly affected when evaluated two- to seven- years after vigorous treatment with medications, and less often with behavior therapy. Only six patients (11%) were symptom free, however, and only three of these were taking no medication. A 9 -to 14 -year follow-up study reported that 8 of 14 adolescents who had received medication treatment were medication free and did not meet OCD criteria; the other six had experienced a chronic, or a relapsing and then chronic course, reported Bolton, Luckie and Steinberg in 1995. Finally, Thomsen and Mikkelsen reported in 1995 that a 1.5 to 5 year follow-up of 23 children and adolescents who had recieved drug treatment found that four were free of OCD, eight had subclinical symptoms and the remaining 11 had chronic or episodic OCD. Larger studies from multiple sites are needed to establish accurately the prognosis associated with modern treatment methods.

In community-identified cases, remission, or a course marked by long, symptom-free periods, seems to be the rule. The apparent frequency of this benign course is probably due to the limited diagnostic validity of interviews conducted by lay interviewers and to the large proportion of milder cases in community sample. According to Nelson and Rice in 1997, only 19% (56 of 291 subjects) meeting OCD criteria during their first lay inerview met these criteria duing a lay interview conducted one year later.



Patients with OCD are at high risk of having comorbid (co-existing) major depression and other anxiety disorders. In a series of 100 OCD patients who were evaluated by means of a structured psychiatric interview, the most common concurrent disorders were: major depression (31%), social phobia (11%), eating disorder (8%), simple phobia (7%), panic disorder (6%), and Tourette's syndrome (5%). In Koran et al.'s 1998 Kaiser Health Plan study, 26% of patients had no comorbid psychiatric condition diagnosed during the one year study period -- 37% had one and 38% had two or more comorbid conditions. These proportions did not differ substantially between men and women. The most commonly diagnosed comorbid conditions were major depression, which affected more than one-half, other anxiety disorders, affecting one-quarter, and personality disorders, diagnosed in a little more than 10%. Panic disorder and generalized anxiety disorder were the most common anxiety disorders. Bipolar mood (manic-depressive) disorder was uncommon, but schizophrenia was rare. Except for eating disorders, which were diagnosed in 1 in 20 women, the rates of specific comorbid conditions were not strkingly different between men and women.

OCD seems to be associated with a mildly increased risk for alcohol abuse and dependence. Rates of OCD observed among alcoholic patients admitted to inpatient and outpatient treatment programs exceed the rate in the general population, but not to the extent suggested by Karno et al.'s study in 1988, which attributed alcohol abuse or dependence to 24% of OCD subjects.

Reports of the lifetime rate of body dysmorphic disorder (fear of imagined ugliness) in OCD patients are also prevalent, as well as findings by Barsky in 1992 indicating that patients with hypochondriasis have an elevated lifetime prevalence rate of OCD compared to medical outpatients from the same clinic. Eating disorders may be more common in OCD patients than in the general population, but the data are sparse. According to Rothenberg in 1990, OCD symptoms are common in patients with anorexia nervosa, second only to depressive disorders. Trichotillomania (compulsive hair pulling with bald spots) is another comorbidity of OCD, as is Tourette's syndrome (the combination of behavioral and vocal tics).

Quality of Life


OCD impairs patients' quality of life. In a study of 60 patients, Koran, Thienemann and Davenport reported in 1996 that medication-free patients with moderate to severe OCD reported worse social functioning and performance in work and other activities than the general population and than patients with diabetes. The more severe the OCD, the more impaired the patients' social functioning, even after controlling for effects of concurrent depression. Moreover, Rasmussen and Eisen noted in 1992 that another indicator of reduced quality of life is lower likelihood of OCD patients marrying.

The high personal cost of OCD is mirrored in high social costs. The estimated 1990 direct costs of OCD to the United States economy were $2.1 billion, and the indirect cost (i.e., lost productivity) $6.2 billion, reported Dupont et al. in 1995. If a greater proportion of individuals with OCD were in treatment, the direct costs would have been considerable higher. For example,according to Nestadt et al. in 1994, among a random sample of the Baltimore study participants, only 1 of 15 individuals (7%) whom a psychiatrist judged to need treatment was receiving it. Rasmussen and Eisen reported in 1988 that the delay between symptom onset and first seeking care is often prolonged by a mean of seven years, while Marks in 1992 reported 10 years. Even with much treatment foregone, OCD accounted for almost 6% of the estimated 1990 cost of all mental illness. High social costs are also reflected in the high rates of unemployment in OCD patients and receipt of disability and welfare payments, reported Leon, Portera and Wissman in 1995. Family members suffer as well. Many studies indicate that patients' symptoms may create disharmony, angry or anguished demands for participating in rituals, a draining dependency, restricted access to rooms or living space, difficulty in taking holidays and intereference with work obligations.

Some Pharmacological Treatments of OCD

 Retrieved From: 
Stanford Med. School

The mechanism of action of the drugs effective in treating OCD (clomipramine, a non-selective serotonin reuptake inhibitor, and the selective serotonin reuptake inhibitors [SSRIs]: citalopram, fluoxetine, fluvoxamine, sertraline and paroxetine) has given rise to the hypothesis that deficient serotonin function is a key element in the pathophysiology of OCD. These drugs block serotonin reuptake by the pre-synaptic neuron, thereby increasing serotonin availability at post-synaptic receptors. The serotonin hypothesis is also supported by the observation that m-CPP (a metabolite of trazodone), which is a partial agonist at serotonin receptor types 1A, 1D and 2C, exacerbates OCD.

About 40% to 60% of patients will respond to clomipramine or to any particular SSRI, and one cannot predict which patient will respond to which drug. A trial of 10-12 weeks at the maximum comfortably tolerated dose is necessary to determine whether a given drug is producing a clinically meaningful response. Direct, controlled comparison studies have found fluvoxamine, paroxetine and sertraline equal in efficacy to clomipramine, the first drug that was demonstrated to be effective in treating OCD.

Dr. Koran's clinical practice is to push the patient in weekly increments to the maximum easily tolerated SSRI (or clomipramine) dose, since it is not possible to predict the dose that will prove effective for an individual patient. For fluvoxamine, he starts the patient at 50 mg/day (25 mg/day for patients who are "sensitive to drugs"), and increases the dose every 5 to 7 days by 50 mg/day to a maximum daily dose of 300 mg/day if possible.
Over 10-12 weeks, symptoms decrease by about 40% to 50% or more in about 60% of patients. Disappearance of all symptoms rarely occurs. Benefit is usually noticeable after 6 weeks, but may take 8 weeks to begin. Non-responders to one SSRI may respond to another or to behavior therapy. Partial responders may benefit further from potentiating (augmenting) drugs or from adding behavior therapy (exposure and response prevention, or cognitive approaches). In addition, reports exist of cases successfully treated with buspirone (60 mg), clonazepam (6.5 mg), trazodone (plus tranylcypromine) and venlafaxine, but these drugs should not be used as single-agent therapy until other, better supported medications have been tried. Clozapine, carbamazepine, lithium, clonidine, stimulants, ECT, sleep deprivation, and bright light therapy are not effective.

Drug therapy should be continued indefinitely, since the available data suggest that patients' symptoms will return within one to two months after medications are stopped, even after two years of successful pharmacotherapy. A recent study suggests that 20% of patients who discontinue a successful drug will not respond when the drug is restarted. Available data suggest, but do not prove, that providing behavior therapy while the patient is taking medication may delay or prevent relapse when medication is discontinued. A number of drugs appear to act as potentiators or augmentors of SSRIs, although the data are limited, but controlled trials of potentiating strategies are sorely needed. OCD patients who have comorbid tics or schizotypal personality are unlikely respond to clomipramine or an SSRI alone, but usually will respond to combining one of these drugs with a modest dose of a neuroleptic such as haloperidol, pimozide or risperidone.

In patients who have not responded to an anti-OCD medication or whose response has been inadequate (about 40% of any large series of patients), the clinician can consider adding one of the following drugs: risperidone 0.5-6.0 mg/day; buspirone 60-90 mg/day; olanzapine 2.5-20 mg/day (weight gain is a problem); trazodone 150-600 mg/day; or, L-tryptophan 2 gm twice daily, plus pindolol 2.5 mg three times daily, plus niacinamide 500 mg daily. One starts with a small dose and increases the dose weekly to the likely therapeutic range, as necessary and as tolerated. Response should be evident within two weeks at a given dose, except for trazodone and the L-tryptophan combination, which may take four to six weeks to produce a substantial effect.

For severely anxious OCD patients, gabapentin 300-3600 mg/day or clonazepam 1-4 mg/day or lorazepam 1-4 mg/day are often helpful. No data support the practice of combining two SSRIs. However, European clinicians are combining clomipramine 50-150 mg with fluvoxamine (50-150 mg), fluoxetine (20-40 mg), sertraline (50-100 mg) or citalopram 40 mg/day and claiming success in many patients unresponsive to either drug alone. When clomipramine is combined with any SSRI other than citalopram, one must monitor blood levels of clomipramine and desmethylclomipramine to avoid cardiac and CNS toxicity. Aim for clomipramine levels of 225-350 ng/ml and combined clomipramine and desmethylclomipramine levels of < or = to 500 ng/ml in blood samples drawn about 12 hours after a dose; steady state takes two to three weeks to achieve. Note that Asian patients may require smaller doses of clomipramine than Caucasians. Unpleasant side effects such as sedation, sexual dysfunction, and weight gain (20-30 lbs.) can lead patients to discontinue clomipramine or SSRIs. Rare reports of akathisia, bleeding, easy bruising and dyskinesias exist. A variety of management strategies can be implemented. Anorgasmia or reduced libido may respond to bupropion 75-150 mg/day, buspirone 15-60 mg, amantadine 100-400 mg/day, methylphenidate 10-20 mg/day, dexedrine 5-10 mg/day or yohimbine 5.4-16.2 mg; additional drugs that may help anorgasmia include sildenafil, mirtazapine and nefazodone. Queasiness is usually transient (weeks) and can be minimized by lowering the dose and titrating up slowly. Diarrhea may respond to taking lactobacillus acidophilus capsules once or twice daily.

Wednesday, May 19, 2010

Short Description of the Central Nervous System (CNS)

It is composed of the brain and spinal cord. The CNS is surrounded by bone-skull and vertebrae. Fluid and tissue also insulate the brain and spinal cord.

Areas of the brain. The above image is from

The brain is composed of three parts: the cerebrum (seat of consciousness), the cerebellum, and the medulla oblongata (these latter two are "part of the unconscious brain").
The medulla oblongata is closest to the spinal cord, and is involved with the regulation of heartbeat, breathing, vasoconstriction (blood pressure), and reflex centers for vomiting, coughing, sneezing, swallowing, and hiccuping. The hypothalamus regulates homeostasis. It has regulatory areas for thirst, hunger, body temperature, water balance, and blood pressure, and links the Nervous System to the Endocrine System. The midbrain and pons are also part of the unconscious brain. The thalamus serves as a central relay point for incoming nervous messages.

The cerebellum is the second largest part of the brain, after the cerebrum. It functions for muscle coordination and maintains normal muscle tone and posture. The cerebellum coordinates balance.

The conscious brain includes the cerebral hemispheres, which are are separated by the corpus callosum. In reptiles, birds, and mammals, the cerebrum coordinates sensory data and motor functions. The cerebrum governs intelligence and reasoning, learning and memory. While the cause of memory is not yet definitely known, studies on slugs indicate learning is accompanied by a synapse decrease. Within the cell, learning involves change in gene regulation and increased ability to secrete transmitters.

The Brain 

During embryonic development, the brain first forms as a tube, the anterior end of which enlarges into three hollow swellings that form the brain, and the posterior of which develops into the spinal cord. Some parts of the brain have changed little during vertebrate evolutionary history. Click here to view an diagram of the brain, and here for a clickable map of the brain.

Parts of the brain as seen from the middle of the brain. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates ( and WH Freeman (, used with permission.
Vertebrate evolutionary trends include
  1. Increase in brain size relative to body size.
  2. Subdivision and increasing specialization of the forebrain, midbrain, and hindbrain.
  3. Growth in relative size of the forebrain, especially the cerebrum, which is associated with increasingly complex behavior in mammals.

The Brain Stem and Midbrain

The brain stem is the smallest and from an evolutionary viewpoint, the oldest and most primitive part of the brain. The brain stem is continuous with the spinal cord, and is composed of the parts of the hindbrain and midbrain. The medulla oblongata and pons control heart rate, constriction of blood vessels, digestion and respiration.
The midbrain consists of connections between the hindbrain and forebrain. Mammals use this part of the brain only for eye reflexes.

The Cerebellum


The cerebellum is the third part of the hindbrain, but it is not considered part of the brain stem. Functions of the cerebellum include fine motor coordination and body movement, posture, and balance. This region of the brain is enlarged in birds and controls muscle action needed for flight.

The Forebrain


The forebrain consists of the diencephalon and cerebrum. The thalamus and hypothalamus are the parts of the diencephalon. The thalamus acts as a switching center for nerve messages. The hypothalamus is a major homeostatic center having both nervous and endocrine functions.
The cerebrum, the largest part of the human brain, is divided into left and right hemispheres connected to each other by the corpus callosum. The hemispheres are covered by a thin layer of gray matter known as the cerebral cortex, the most recently evolved region of the vertebrate brain. Fish have no cerebral cortex, amphibians and reptiles have only rudiments of this area.
The cortex in each hemisphere of the cerebrum is between 1 and 4 mm thick. Folds divide the cortex into four lobes: occipital, temporal, parietal, and frontal. No region of the brain functions alone, although major functions of various parts of the lobes have been determined.

The major brain areas and lobes. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates ( and WH Freeman (, used with permission.
The occipital lobe (back of the head) receives and processes visual information. The temporal lobe receives auditory signals, processing language and the meaning of words. The parietal lobe is associated with the sensory cortex and processes information about touch, taste, pressure, pain, and heat and cold. The frontal lobe conducts three functions:
  1. motor activity and integration of muscle activity
  2. speech
  3. thought processes

Functional areas of the brain. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates ( and WH Freeman (, used with permission.
Most people who have been studied have their language and speech areas on the left hemisphere of their brain. Language comprehension is found in Wernicke's area. Speaking ability is in Broca's area. Damage to Broca's area causes speech impairment but not impairment of language comprehension. Lesions in Wernicke's area impairs ability to comprehend written and spoken words but not speech. The remaining parts of the cortex are associated with higher thought processes, planning, memory, personality and other human activities.

Parts of the cerebral cortex and the relative areas that are devoted to controlling various body regions. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates ( and WH Freeman (, used with permission.

Friday, May 7, 2010

Types of Aphasia

American Stroke Association

Types of Aphasia 

Retrieved From: American Stroke Association 

Excerpted from "The Language of Aphasia," Stroke Connection Magazine, May/June 2003 (Science Update August 2009)

Aphasia | Comprehension | Wernicke's | Broca's 

Global | Remember

Language is much more than words. It involves our ability to recognize and use words and sentences. Much of this capability resides in the left hemisphere of the brain. When a person has a stroke or other injury that affects the left side of the brain, it typically disrupts their ability to use language.

Through language, we:

  • Communicate our inner thoughts, desires, intentions and motivations.

  • Understand what others say to us.

  • Ask questions.

  • Give commands.

  • Comment and interchange.

  • Listen.

  • Speak.

  • Read.

  • Write.
A stroke that affects the left side of the brain may lead to aphasia, a language impairment that makes it difficult to use language in those ways. Aphasia can have tragic consequences.

People with aphasia:

  • May be disrupted in their ability to use language in ordinary circumstances.

  • May have difficulty communicating in daily activities.

  • May have difficulty communicating at home, in social situations, or at work.

  • May feel isolated.
Scientists and clinicians who study how language is stored in the brain have learned that different aspects of language are located in different parts of the left hemisphere. For example, areas in the back portions allow us to understand words. When a stroke affects this posterior part of the left hemisphere, people can have great difficulty understanding what they hear or read.
Imagine going to a foreign country and hearing people speaking all around you. You would know they were using words and sentences. You might even have an elemental knowledge of that language, allowing you to recognize words here and there, but you would not have command of the language and couldn’t follow most conversation. This is what life is like for people with comprehension problems.

People with comprehension problems:

  • Know that people are speaking to them.

  • Can follow some of the melody of sentences — realizing if someone is asking a question or expressing anger.

  • May have great difficulty understanding specific words.

  • May have great difficulty understanding how words go together to convey a complete thought.
Wernicke's Aphasia

People with serious comprehension difficulties have what is called Wernicke’s aphasia and:

  • Often say many words that don’t make sense.

  • May fail to realize they are saying the wrong words; for instance, they might call a fork a “gleeble.”

  • May string together a series of meaningless words that sound like a sentence but don’t make sense.

  • Have challenges because our dictionary of words is shelved in a similar region of the left hemisphere, near the area used for understanding words.
Broca's Aphasia
When a stroke injures the frontal regions of the left hemisphere, different kinds of language problems can occur. This part of the brain is important for putting words together to form complete sentences. Injury to the left frontal area can lead to what is called Broca’s aphasia. Survivors with Broca's aphasia:

  • Can have great difficulty forming complete sentences.

  • May get out some basic words to get their message across, but leave out words like “is” or “the.”

  • Often say something that doesn’t resemble a sentence.

  • Can have trouble understanding sentences.

  • Can make mistakes in following directions like “left, right, under, and after.”
“Car…bump…boom!” This is not a complete sentence, but it certainly expresses an important idea. Sometimes these individuals will say a word that is close to what they intend, but not the exact word; for example they may say “car” when they mean “truck.”
A speech pathologist friend mentioned to a patient that she was having a bad day. She said, “I was bitten by a dog.” The stroke survivor asked, “Why did you do that?” In this conversation, the patient understood the basic words spoken, but failed to realize that the words of the sentence and the order of the words were critical to interpreting the correct meaning of the sentence, that the dog bit the woman and not vice verse.

Global Aphasia

When a stroke affects an extensive portion of the front and back regions of the left hemisphere, the result may be global aphasia. Survivors with global aphasia:

  • May have great difficulty in understanding words and sentences.

  • May have great difficulty in forming words and sentences.

  • May understand some words.

  • Get out a few words at a time.

  • Have severe difficulties that prevent them from effectively communicating.
Remember, when someone has aphasia:

  • It is important to make the distinction between language and intelligence.

  • Many people mistakenly think they are not as smart as they used to be.

  • Their problem is that they cannot use language to communicate what they know.

  • They can think, they just can’t say what they think.

  • They can remember familiar faces.

  • They can get from place to place.

  • They still have political opinions, for example.

  • They may still be able to play chess, for instance.
The challenge for all caregivers and health professionals is to provide people with aphasia a means to express what they know. Through intensive work in rehabilitation, gains can be made to avoid the frustration and isolation that aphasia can create.