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Abstract: White matter abnormalities in patients with OCD and their first-degree relatives
posted Friday, 3 October 2008
Am J Psychiatry 2008;165:1308-1315
White Matter Abnormalities in Patients With Obsessive-Compulsive Disorder and Their First-Degree Relatives
Menzies L, Williams GB, Chamberlain SR, Ooi C, Fineberg N, Suckling J, Sahakian BJ, Robbins TW, Bullmore ET.
Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.
OBJECTIVE: Obsessive-compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysconnectivity of large-scale brain systems. The extent of white matter abnormalities in OCD is unknown, and the genetic basis of this disorder is poorly understood. The authors used diffusion tensor imaging, a magnetic resonance imaging technique, for examining white matter abnormalities in brain structure through quantification of water diffusion, to confirm whether white matter abnormalities exist in OCD. They also explored whether such abnormalities occur in healthy first-degree relatives of patients, indicating they may be endophenotypes representing increased genetic risk for OCD.
METHOD: The authors used diffusion tensor imaging to measure fractional anisotropy of white matter in 30 patients with OCD, 30 unaffected first-degree relatives, and 30 matched healthy comparison subjects. Regions of significantly abnormal fractional anisotropy in patients in relation to healthy comparison subjects were identified by permutation tests. The authors assessed whether these abnormalities were also evident in the first-degree relatives. A secondary region-of-interest analysis was undertaken to assess the extent of replication between our data and previous relevant literature.
RESULTS: Patients with OCD demonstrated significantly reduced fractional anisotropy in a large region of right inferior parietal white matter and significantly increased fractional anisotropy in a right medial frontal region. Relatives also exhibited significant abnormalities of fractional anisotropy in these regions.
CONCLUSIONS: These findings indicate that OCD is associated with white matter abnormalities in parietal and frontal regions. Similar abnormalities in unaffected first-degree relatives suggest these may be white matter endophenotypes for OCD.
(Text has been reformatted for visual clarity; ed.)
© 2008 American Psychiatric Association
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Action-potential
Wave of electrochemical activity generated by the flow of positively charged ions across the neuronal membrane which causes a neuron to 'fire'- Click page link for more information -
Affective disorders
Mental disorders characterized by dramatic changes or extremes of mood - depression, mania, or both - including depression, bipolar disorder (manic depression), and schizo affective disorders.- Click page link for more information -
Alleles
An alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome.- Click page link for more information -
Amygdalae
Two almond-shaped groups of neurons - there is one amygdala (Greek for almond) in each brain hemisphere. They have the primary role in processing and storing memories of emotional reactions.Part of the Limbic System the amygdalae trigger an instant fear reaction to perceived threats, real or imagined.
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Anterior cingulate cortex
Involved in empathy, emotions, cognitive control (attention, conflict monitoring during information processing) and plays a role in stimulus reinforcement learning and reward-guided selection of actions.Also controls autonomic functions such as heart rate and blood pressure in the context of current behavior.
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Autonomic arousal
Arousal of the autonomic nervous system which regulates many bodily functions and produces the physical symptoms of stress including the 'fight-or-flight' response.Brain-derived neurotrophic factor
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Client-centered therapy
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Type of psychotherapy emphasizing the important role of thinking in how we feel and what we do.Based on the concept that our thoughts cause our feelings and behaviors, not external things like people, situations, and events. The benefit of this fact is that we can change the way we think to feel/act better even if the situation does not change.
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Corticotropin-releasing factor
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Epidemiological studies describing population characteristics which collect data at one point in time and then consider relationships between observed characteristics.. Because they don't look at time trends they cannot establish causes.
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Mood disorder within the depression spectrum. Considered a chronic depression, but less severe than major depression.- Click page link for more information -
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Epigenetic inheritance
Process by which environmental factors like diet, stress, and ante/post-natal maternal factors can change gene function without altering the DNA sequence. These changes may remain through cell divisions and may also be passed down through multiple generations.- Click page link for more information -
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Suppression of the expression of previously learned fear by repeated exposure to the object of fear without negative consequences. Also called 'inhibitory learning'- Click page link for more information (
) -First-degree relative
A parent, sibling or child of an individual.Gamma-Aminobutyric Acid (GABA)
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Note 1: Benzodiazepines (Valium® etc) do not increase brain GABA levels, but increase the sensitivity of GABA receptors.
Note 2: GABA does not normally penetrate the Brain-Blood-Barrier (the BBB tends to pull GABA from the brain into the blood stream (Kakee A, 2001)) so GABA supplements are, at best, expensive placebos.
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Glial Cells
Support cells in the brain and spinal cord which provide physical and nutritional support for neurons, form the blood-brain barrier, clear dead cells and other debris, insulate neurons and, as part of the immune system, protect the brain from microorganisms.Long thought not to conduct electrical impulses as the neurons do, there is growing evidence that they do modulate neurotransmission.
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Haplotype
A group of alleles of different genes on a single chromosome that are so closely linked that they are usually inherited as a unit.- Click page link for more information -
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Because genes are either dominant or recessive, the genetic makeup (genotype) of an organism cannot always be determined by physical appearance alone.
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Anatomical structures that perform the same function in different biological species having evolved from the same structure in a shared ancestor species.Hypothalamus
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Signaling molecules critical to the functioning of the immune system.A recombinant form of IL-2 has been approved as an anti cancer drug and and may have anti viral properties. Changes in mental states including irritability, confusion, or depression are a known side-effect.
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Mathematical technique to amalgamating, summarizing, and reviewing previous quantitative research to arrive at one overall measure of treatment effect.A weakness of the method is that sources of bias in the original research are not controlled by the method. A good meta-analysis of badly designed studies will still result in bad statistics.
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Mindfulness meditation/ psychotherapy
Mindfulness is the practice of becoming more aware of the present moment, rather than dwelling in the past or projecting into the future. It generally involves a heightened awareness of sensory stimuli (really noticing your breathing, feeling the sensations of your body, etc); and being 'in the now'. Principles may be combined with the concepts of Cognitive-Behavior Therapy (CBT) as Mindfulness-based Psychotherapy.- Click page link for more information -
Narrative Exposure Therapy
Therapy developed to treat PTSD. Based on cognitive behavioral exposure therapy, it adapts classical exposure therapy to meet needs of traumatized survivors of war and torture.Survivors are asked to describe what happened to them in great detail, focusing on what they saw, heard, smelt, etc, and their feelings and thoughts at the time. Initially, sessions are distressing, but as they are long enough to allow habituation, distress levels diminish towards the end and more and more details are recalled.
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Neurogenesis
Process by which new neurons are generated after the postnatal stage of development. It appears to only occur in two areas of the brain, the hippocampus and the olfactory bulbs. Hippocampal neurogenesis is thought to counter anxiety and depression.- Click page link for more information -
Neuropeptide
One of about 100 peptides including endorphins, enkephalins, oxytocin and vasopressin which mediate brain function by regulating gene expression, local blood flow and synaptogenesis. The neuropeptides Cholecystokinin, Substance P and Neuropeptide Y have been linked to anxiety and depressive disorders.- Click page link for more information -
Neuroplastic
The brain's ability to reorganize itself by forming new neural connections.- Click page link for more information -
Nucleus accumbens
Twin brain structures (one in each hemisphere) involved in reward, laughter, pleasure, addiction, fear, and the placebo effect.- Click page link for more information -
Polymorphism
Natural variations in a gene, DNA sequence, protein, or chromosome.-Click page link for more information-
Prefrontal Cortex
Area of the brain's frontal lobes involved in planning complex cognitive behaviors, the expression of personality and social behavior.- Click page link for more information -
Prospective study
Tests a specific question, usually about how a specific exposure(s) affects a specific outcome(s) by recruiting appropriate participants and checks the outcomes over the following months or years.Psychodynamic psychotherapy
Talking therapy used to help a person find relief from emotional pain. It is based on the theories and techniques of Freudian/Jung style psychoanalysis. However, practitioners don't necessarily accept the 'classical' psychoanalysis theory that emotional conflicts are primarily sexual in nature.Receptor
Short-lived protein molecules embedded in the cell wall of neurons, especially of their synapses, to which neurotransmitters attach to initiate an action. Also called ´binding sites´- Click page link for more information -
Receptor agonist
A chemical which is able to bind to receptors of a neurotransmitter and trigger the same biological response as that neurotransmitter.Receptor antagonist
A drug that is so similar chemically to a neurotransmitter that it is capable of binding to a receptor for the neurotransmitter but which does not trigger the biological response of that neurotransmitter. By blocking its receptors the antagonist disrupts or inhibits the action of the neurotransmitter.Retrospective study
Research using data on exposures and/or outcomes that have already been collected through medical records or as part of another study. Such data may not be as reliable as data collected prospectively, as it relies on the accuracy of records made at the time, and on people’s recall of past events, which can be inaccurate (referred to as recall bias).Safety behavior
Behavior undertaken to reduce anxious thoughts, or to keep yourself 'safe' from imagined threats, or to hide your anxious state from others. Examples include constant monitoring of breathing or heart rate, shopping during quiet retail hours, taking precautionary tranquillizers "just in case," taking circuitous routes to avoid highways or bridges when driving, sitting close to exits, avoiding eye contact, playing with keys to hide trembling hands.Seasonal affective disorder
A type of depression triggered by the seasons. The most common type is winter-onset depression (aka Winter blues), but some also regularly become depressed at the start of spring-summer.- Click page link for more information -
Serotonin syndrome
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Serotonin transporter
A protein that transports the neurotransmitter serotonin across cell membranes.- Click page link for more information -
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Major stressors such as: death of relative (incl. miscarriage), friend, or pet; serious illness or injury, surviving a disaster; marriage, separation, divorce, relationship breakup; birth or adoption of a child; moving house or school; new job or promotion, unemployment or retirement;Somatization disorder
Manifests as chronic, persistent complaints of varied physical symptoms that have no identifiable organic origin or basis. Often co morbid with other psychological disorders, particularly anxiety or mood disorders, plus irritable bowel syndrome and chronic pain. Occurs in 0.2% to 2% of females and 0.2% of males. Also known as Briquet's disorder.Sympathetic nervous system
The part of the nervous system which controls the body’s internal, involuntary processes including breathing, digestion, blood vessel tone, heart rate, etc. It also mediates the fight-or-flight response.Subgenual cingulate
Brain region high in serotonin transporter-binding sites, with strong projections to the hypothalamus and brain stem. Modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. May be critical for modulating widespread behavioral changes mediated by the cortex. Volume is often decreased in mood disorders patients.Also known as Brodmann area 25.
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Synapses
Gaps between neurons through which "information" flows from one neuron (brain cell) to another.- Click page link for more information -
Thalamus
Regulates sleep and awake states, arousal and awareness. Processes and relays sensory information to the cerebral cortex where they are experienced as sensations of pain, touch, or temperature. Damage to the thalamus can produce permanent coma.- Click page link for more information -
Tumor necrosis factor-α
A cytokine which has wide range of pro inflammatory actions and induce necrosis (death) of tumor cells. Exacerbates chronic inflammatory autoimmune diseases such as rheumatoid arthritis.Blood plasma levels are raised in patients with depression. Research had shown that antidepressants reduce its expression.
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White matter
Regions of the brain and spinal cord largely composed of nerve fibers (axons) sheathed in insulating myelin composed of lipids (fats) which give them their color.White matter abnormalities (hyperintensities):
Damage to the myelin insulation. May be inherited, the result of disease (Multiple Sclerosis) or physical injury, stroke etc. Most brains accumulate some WM abnormalities with age.
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