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Genetic predisposition plays role in anxiety disorders

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posted Wednesday, 27 August 2008

Finnish researchers have identified genes which may predispose to anxiety disorders. Their research focussing on genes that influence human behavior found genes which show a statistical association with specific anxiety disorders. The research was conducted as part of the Academy of Finland Research Programme on Neuroscience (NEURO) and will be published in the October issue of the journal Biological Psychiatry.

Previously the team lead by Academy of Finland Research Fellow Iiris Hovatta have explored the genetic background of anxiety in experimental models. The current study follows up on these findings in humans using data collected as part of national Health 2000 Survey of 321 individuals diagnosed with anxiety disorder and 653 matched controls.

Hovatta says it was interesting that different genes showed evidence for association to specific types of anxiety disorders, such as panic disorder, social phobias or generalized anxiety disorder.

Specific alleles and haplotypes of six of the examined genes revealed some evidence for an association. The most significant evidence for an association with different anxiety disorder subtypes were with ALAD (d-aminolevulinate dehydratase) in social phobia, DYNLL2 (dynein light chain 2) in generalized anxiety disorder, and with PSAP (prosaposin) in panic disorder.

"Environmental factors, such as stressful life events, may trigger an anxiety disorder more easily in people who have a genetic predisposition to the illness," Hovatta says. The focus in the team's further studies will be to understand the molecular and cellular processes that link these genes to the regulation of anxiety behavior.

Currently, the team's international collaborators in Spain and the United States are trying to replicate these findings in their anxiety disorder datasets to see whether the identified genes also predispose to anxiety disorders in other populations.

A closer understanding of the genetics and neurobiology of anxiety disorders is expected to help improve treatment of the illness using both drugs and therapy-based approaches. For the time being, no targeted drugs are available for the treatment of anxiety disorders. Current medications benefit only about 50 percent of anxiety patients.

Donner J, Pirkola S, Silander K, et al. An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders Biol Psychiatry 2008; doi:10.1016/j.biopsych.2008.06.002 [Abstract]

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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'
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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.
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Alleles

An alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome. There are two alleles for each trait.
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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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Brain-derived neurotrophic factor

Protein required for the growth and survival of nerve cells during development, and for maintenance of adult nerve cells. Studies have shown that some neurotrophic factors can trigger regrowth of damaged nerve cells and stimulate growth and differentiation of new neurons and synapses in the hippocampus.
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Cognitive-behavioral therapy (CBT)

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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Clinical trial-Phase 1

The first test in humans of a new treatment to see if it is safe to use in people.
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Compassion meditation

Based on Tibetan Buddhism techniques. Trains the mind to optimize the way it perceives relationships with others. Experienced practitioners are able to alter brain functioning to boost positive emotions, and enhance their immune systems.

Related to Mindfulness Meditation/Psychotherapy.
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Corticotropin-releasing factor

A polypeptide hormone and neuro- transmitter involved in the stress response.

CRF hyper secretion is believed to contribute to hyperactivity of the hypothalamic-pituitary-adrenal axis in depressed patients. Hyper secretion has also been implicated in anxiety.
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Cortisol

The most potent of the stress hormones. Synthesized from cholesterol by the adrenal glands. Increases blood pressure, blood sugar levels and suppresses immune function.
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Dentate gyrus

Part of the hippocampus. Thought to contribute to formation of new memories and is one of the few brain regions where neurogenesis occurs. Has a role in recognizing the differences that make each place unique. Processing errors may play a role in deja vu.
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Depression - Atypical

Defined by the ability to feel better temporarily in response to positive life events, plus any two of the following criteria: excessive sleep, overeating, a feeling of heaviness in the limbs and a sensitivity to rejection. Despite the name, it is actually the most common form of depression.
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Depression - Clinical/Major

Characterized by a pervasive, unremitting low mood and loss of interest or pleasure in usual activities. In addition there are other physical and mental symptoms that may include fatigue, difficulty with concentration and memory, feelings of hopelessness and helplessness, headaches, body aches, and thoughts of suicide.
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Epigenetics

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.
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First-degree relative

A parent, sibling or child of an individual.

Gamma-Aminobutyric Acid (GABA)

The major inhibitory neurotransmitter of the central nervous system. Dampens brain activity and promotes a state of calm.

An amino acid produced in the brain as a by-product of the Krebs glucose metabolism cycle which powers brain cells.

Note 1: Benzodiazepines (Valium® etc) do not increase brain GABA levels, but increase the sensitivity of GABA receptors.

Note 2: GABA does not penetrate the Brain-Blood-Barrier so GABA supplements are, at best, expensive placebos.
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Heterozygote, Homozygote

Heterozygote: Any organism which has two differing forms of a particular gene for a specific trait, one inherited from each parent.

Homozygote: Any organism which has two identical forms of a particular gene for a specific trait, one inherited from each parent.

Because genes are either dominant or recessive, the genetic makeup (genotype) of an organism cannot always be determined by physical appearance alone.

Hippocampus

A seahorse shaped sheet of neurons laying next to the Amygdalae. Regulates emotions and short term memory.
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Homologous

Anatomical structures that perform the same function in different biological species having evolved from the same structure in a shared ancestor species.

Hypothalamus

Regulates homeostasis, the maintenance of the body's status quo by producing hormones which control: Body temperature, Hunger, Moods, Sex drive, Sleep and Thirst.
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Interpersonal psychotherapy

Time-limited psychotherapy focusing on the interpersonal context and building interpersonal skills. Based on the belief that interpersonal factors may contribute heavily to psychological problems. Distinguished from other forms of therapy in its emphasis on the interpersonal rather than the intra psychic.
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Meta-analysis

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 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.
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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.
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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.
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Neuroplastic

The brain's ability to reorganize itself by forming new neural connections.
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Prefrontal Cortex

Area of the brain's frontal lobes involved in planning complex cognitive behaviors, the expression of personality and social behavior.
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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´
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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.

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.
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Serotonin transporter

A protein that transports the neurotransmitter serotonin across cell membranes.
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Synapses

Gaps between neurons through which "information" flows from one neuron (brain cell) to another.
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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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