PSYC 415 -- Notes on Anxiety Disorders, Etc. Anxiety Disorders panic disorder characterized by panic (anxiety) attacks shortness of breath clammy sweat dizziness, faintness feelings of unreality sometimes mistaken for a heart attack anticipatory anxiety - the fear of an impending panic attack associated with secondary agoraphobia for fear of having a public attack risk: just under 2% (book) about twice as common in women as in men (figure) generalized anxiety disorder characterized by excessive (free-floating) anxiety, worry, and dread risk: about 3% about twice as common in women as in men social anxiety disorder (social phobia) excessive fear of being exposed to public scrutiny avoidance of social situations intense anxiety and distress during unavoidable social situations risk: about 5% equally common in men and women possible causes genetic predisposition - family studies and twin studies panic disorder - at one time a single dominant gene was proposed inheritance pattern is not so strong in other anxiety disorders the serotonin transporter gene has been implicated panic attacks can be induced in people susceptible to them by infusion of lactic acid or inhalation of carbon dioxide has allowed PET scanning studies to be done dramatically incr. blood flow & glucose utilization in temporal poles the amygdala is implicated also the ant. cingulate cx and orbitofrontal cx - decr. activation treatment traditional anxiolytic drugs barbiturates benzodiazepines (Librium, Valium, Xanax, etc.) alcohol - often self-prescribed esp. for social anxiety these drugs all activate the GABA-A receptor the role of the amygdala in the GABA-A story high concentration of GABA-A receptors in the amygdala local infusions of benzodiazepines produce anxiolytic effects local infusions of GABA antagonists blocks the anxiolytic effects of systemically administered benzodiazepines the GABA theory of anxiety - due to deficient GABA transmission decreased sensitivity of receptors - due to a decr. no. of receptors? an experiment with cats pregnant cats were given diazepam to expose kittens prenatally produced anxious, fearful kittens with decr. no. of GABA-A receptors a spanner in the works of the GABA theory buspirone is a serotonin agonist anxiolytic but not sedating or ataxigenic drugs of choice lately - SSRIs (e.g., Prozac, Zoloft) cognitive-behavioral therapy (esp. with densitization) is useful anxiety disorders are often comorbid with depression Obsessive-Compulsive Disorder (OCD) definitions obsessions - persistent, irresistible, and disturbing thoughts compulsions - same except with behavior (handwashing, e.g.) risk: 1-2% (slightly more in women) some interesting parallels amphetamine-induced stereotypy in rats "punding" and "tweaking" in amphetamine addicts OCD is associated with Tourette's syndrome characterized by muscular and vocal tics, facial grimaces, pacing, twirling, barking, sniffing, coughing, grunting, repeating specific words, echolalia a tic disorder that starts in childhood (age 5-7 is typical) thought to be an inherited disorder - exact mode of inheritance unknown, and no gene has been identified (may also be sporatic) environmental factors also play a role - streptococcal infections, autoimmune PFC, basal ganglia, cingulate cx, and thalamic circuits have been implicated OCD may be an alternate expression of the Tourette's genotype some people now classify OCD as a tic disorder scanning studies implicate the orbitofrontal cx, cingulate cx, and caudate nuc. direct and indirect output pathways of the neostriatum direct (excitatory) pathway - rapid execution of automatic behaviors indirect (inhibitory) pathway - suppressing automatic behaviors permitting a switch to other adaptive patterns of behavior theory - OCD is due to an imbalance between these two pathways (Saxena) orbitofrontal cx - recognizes situations that have personal significance and activates the excitatory lope of neostriatal output treatment prefrontal leukotomy - disconnecting PFC and cingulate cx from limbic system this can also result in typical symptoms of frontal lobe syndrome, however deep brain stimulation has worked in some patients drugs clomipramine - a tricyclic antidepressant that is fairly 5-HT-specific fluoxetine (Prozac) - an SSRI fluvoxamine (Luvox) - an SSRI so what's serotonin got to do with it? - diagram Autistic Disorders signs - are apparent very early in lige failure to develop normal social reactions failure to develop normal communication abilities repetitive, stereotyped behavior ("stimming") variable degree of cognitive impairment risk: about 0.1% (0.6% for the entire spectrum) 4 times more common in males than females female children are likely to have cognitive impairment w/o social impairment incidence is increasing probably due to incr. awareness and changing diagnostic criteria autism is not linked to socioeconomic status there is no credible evidence that it is linked to childhood vaccinations causes the neofreudian notion that it was due to cold, insensitive, demanding, introverted parents was obviously and totally wrong there is evidence of a genetic predisposition 70% concordance in MZ twins (90% for entire spectrum) 5% concordance in DZ twins (10% for entire spectrum) a large number of genes concerned with neural development are implicated rubella during pregnancy can cause autism, as can certain infections abnormal developmental patterns in association cortex have been found - scanning studies show normal activation in sensory and unimodal assoc. cx but deficient activation in heteromodal assoc. cx and PFC fusiform face area (inferior occipital-temporal assoc. area responsible for recognition of human faces) fails to activate in autistic individuals could be a developmental abnormality in the FFA could be because they have so little experience looking at faces "stimming" resembles the repititive stereotyped behaviors of tic disorders and may be due to increased activation in the caudate nuc. (Fig. 17.8) treatment - cognitive-behavioral therapy is very stongly indicated from as early an age as possible Attention-Deficit Hyperactivity Disorder most common behavioral disorder of childhood difficulty withholding a response - failure of behavioral inhibition act without reflecting - impulsive often show reckless and impetuous behavior - poor judgment let interfering activities intrude into ongoing tasks must be carefully differentiated from normal childhood rambunctiousness makes risk/prevalence/incidence figures suspect book puts risk at 4-5% among gradeschool children boys about 10 times more likely than girls to be diagnosed - as the book points out, this may be more a diagnostic problem than a true gender diff. associated with learning disabilities and conduct disorder about 60% continue to display symptoms as adults - becomes associated with antisocial personality disorder and substance abuse disorder treatment - aimed at symptom control methylphenidate (Ritalin, Concerta, Focalin, Metadate, Methylin) amphetamines (Adderal, Desoxyn) atomoxetine (Strattera) - a NE reuptake inhibitor behavioral therapy possible causes genetic predisposition - heritability estimated to be 75-91% steeper than normal delay of reinforcement gradient due to deficient DA neurotransmission in the reward system (Sagvolden, et al.) immediate Rx is more effective resulting in overactivity delayed Rx is ineffective resulting in frequent behavior switching prefrontal cortex syndrome distractibility forgetfulness impulsivity poor planning hyperactivity perhaps due to deficiency of DA input to PFC from mesocortical system DA activity in the PFC has to be stabilized at just the right level - inverted U function studies on COMT and response to amphetamine in some people amphetamine stimulates positive mood and enhances performance, while in others it has the opposite effect people with the val-val variant of the COMT gene have low levels of brain catecholamines and experience performance enhancement people with the met-met variant of the COMT gene have high levels of brain catecholamines and experience performance impairment there is some evidence from scanning studies of delayed cortical development in children diagnosed with ADHD this may result in impaired communication with and activation of the neostriatum (caudate nuc.) during tasks that require attention and ability to inhibit interfering behavior