Emotion and relative reward processing: an investigation on instrumental successive negative contrast and ultrasonic vocalizations in the rat.

Incentive contrast effects include changes in behavioral responses after a reward upshift (positive contrast) or downshift (negative contrast). Proposed influences on these behavioral changes are emotional state reactions after experiencing or anticipating a change in reward outcome. Rat ultrasonic vocalizations have been shown to be indicators of emotional state during behavior and anticipatory periods. The objective of the present study was to monitor rodent ultrasounds during incentive contrast using a classical runway procedure called instrumental successive negative contrast. The procedure is one that has been used often to examine incentive relativity because of its reliability in measuring negative contrast effects. Rats were trained to run in the alleyway to receive a high (12 pellets) or low magnitude (1 pellet) outcome. The high magnitude was then shifted to the low and running speeds in the alleyway for the reward and USV emission were compared. Replicating previous work, a negative contrast effect was observed with postshift running speeds significantly slower in the shifted group compared to the unshifted group. USVs did not follow the same pattern with an apparent lack of significant differences between the groups following the reward downshift. We also tested another group of animals using a visual predictive cue in the same runway test. When visual cues predicted high or low magnitude outcome, no incentive contrast was found for the running speeds following an outcome downshift, but a weak contrast effect was observed for the USV emission. These results demonstrate a separation between USVs and behavioral indicators of incentive contrast suggesting that concomitant shifts in negative affect may not be necessary for anticipatory relative reward processes.

Psychological features of subjects with idiopathic environmental intolerance.

OBJECTIVES: Idiopathic environmental intolerance (IEI) is associated with unexplained symptoms attributed to non-noxious levels of environmental substances. Clinically, some of the symptoms of IEI overlap with those of panic disorder (PD). We have recently reported a link between IEI and panic responses to a single inhalation of 35% carbon dioxide (CO(2)), a reliable panic induction challenge. This study assessed depression, stress, anxiety, and agoraphobic symptoms among IEI subjects from our previous study versus healthy controls. METHODS: Thirty-six IEI and 37 control subjects with no preexisting psychiatric history were compared on self-report psychological questionnaires. RESULTS: IEI subjects scored significantly higher than controls on the Agoraphobic Cognitions Questionnaire (ACQ), Depression Anxiety Stress Scales (DASS), and Mobility Inventory for Agoraphobia (MI) (Student's t, P<.05). CONCLUSIONS: IEI subjects represent a group with morbidity significantly higher than a control population but less than what would be expected for a clinical psychiatric population.

Idiopathic environmental intolerance: increased prevalence of panic disorder-associated cholecystokinin B receptor allele 7.

BACKGROUND: A growing body of evidence suggests that idiopathic environmental intolerance (IEI) is a psychophysiologic disorder with prominent features of anxiety/panic and somatization, although proponents of a toxicogenic explanation claim, despite a lack of convincing evidence, that symptoms arise from exposure to otherwise nonnoxious environmental agents. Patient behaviour is characterized by strenuous avoidance of perceived triggers to the point of severe impairment of normal social and vocational functioning. IEI proponents claim that previous studies showing a high prevalence of psychopathology in patients with IEI and studies showing panic responses to known panicogenic challenges merely reflect the anxiety-producing result of living with IEI. OBJECTIVE: We explored whether IEI and panic disorder, personality traits, or both shared an underlying neurogenetic basis that would predate the anxiety of IEI symptomatology. The DNA of patients with IEI was examined for the presence of known panic disorder-associated cholecystokinin B (CCK-B) receptor alleles and for personality trait-associated dopamine D4 receptor polymorphisms. METHODS: Eleven patients with typical IEI symptoms were recruited and were individually matched to normal control subjects from an existing bank for age, sex, and ethnic background. Genomic DNA was extracted from peripheral blood samples. CCK-B and dopamine D4 receptor polymorphisms were examined by using standard PCR-based techniques. RESULTS: There was a significantly higher prevalence of the panic disorder-associated CCK-B receptor allele 7 in subjects with IEI (9/22 [40.9%]) compared with control subjects (2/22 [9.1%], P =.037). There was no difference in personality trait-associated polymorphisms of the gene encoding dopamine D4 receptor between patients and control subjects. CONCLUSIONS: These findings provide preliminary evidence that IEI and panic disorder share a common neurogenetic basis, which would predate the anxiety-producing effects of IEI symptoms. Further studies with larger samples are warranted, but these results support previous studies that suggest that panic disorder may account for much of the symptomatology in at least some cases of IEI and provide a basis for rational treatment strategies.

Clinical, biochemical, and genetic characterization of a novel estrogen-dependent inherited form of angioedema.

BACKGROUND: Two genetic forms of hereditary angioedema (HAE) are currently recognized. Both are transmitted in an autosomal dominant manner and are characterized by recurrent episodes of localized angioedema. Involvement of the gut leads to episodes of severe abdominal pain, and laryngeal involvement can lead to airway obstruction and even death. One type results from heterozygosity for a nonexpressed C1 inhibitor allele, and the other results from heterozygosity for a nonfunctional C1 inhibitor allele. OBJECTIVE: This report identifies a third type of HAE, with a unique estrogen-dependent phenotype. METHODS: Detailed medical histories were obtained from family members, and a pedigree was constructed to ascertain the mode of inheritance. Determination of serum complement factors, C1 inhibitor protein, C1 inhibitor function, coagulation factor XII, plasma prekallikrein, high molecular weight kininogen, and selected DNA sequences were performed in affected members by using standard assays. RESULTS: Episodes of angioedema were clinically indistinguishable from those associated with previously described forms of HAE; however, these occurred only during pregnancy or the use of exogenous estrogens. Patients were otherwise asymptomatic, except for one patient who had acetyl salicylic acid/nonsteroidal anti-inflammatory drug-related angioedema later in life. History was available for members spanning 4 generations, and affected individuals were identified in 3 generations. Of 46 family members, phenotype could be determined in 13 members. Seven were affected, and 6 were not. One male of undetermined phenotype was an obligate carrier. The unique estrogen-dependent nature of the phenotype means that the status of several members in the third and fourth generation remains unknown. The disorder appears to be transmitted in an autosomal dominant fashion, although other modes of inheritance cannot be excluded entirely. C1 inhibitor protein, C1 inhibitor function, C2, C4, C1q, coagulation factor XII, prekallikrein, and high molecular kininogen were normal in 3 affected family members during asymptomatic periods. DNA sequencing revealed no abnormality in 3 patients in the coding region of the gene encoding C1 inhibitor or in the 5' flanking regions of the genes encoding C1 inhibitor and factor XII. CONCLUSIONS: This family appears to have a novel form of inherited angioedema that does not result from C1 inhibitor deficiency or dysfunction. The phenotype is uniquely estrogen dependent. Implications for diagnosis and treatment are discussed. Further studies are required to define the exact nature of the genetic abnormality involved.

Idiopathic environmental intolerances: results of challenge studies.

It has been postulated that psychophysiologic mechanisms may account for symptom generation in IEI. In this review, the similarity of IEI and panic disorder symptoms are noted. The results of various challenge studies, both with known panicogenic substances and self-identified triggers, are examined. Available data are consistent with the premise that IEI symptoms have a psychophysiologic basis.

Carbon dioxide inhalation challenges in idiopathic environmental intolerance.

BACKGROUND: Idiopathic environmental intolerance (IEI) is associated with unexplained physical symptoms, which overlap considerably with those of panic disorder (PD). OBJECTIVE: This study tested the hypothesis that patients with symptoms to suggest IEI exhibit features of PD in response to nonnoxious environmental stimuli. METHODS: A single-blind, case-control 35% carbon dioxide inhalation challenge was conducted at a university-based occupational health unit with the use of standardized psychologic questionnaires involving 36 patients with IEI and 37 healthy control subjects. The main outcome measures included panic attack symptoms and scores on the Anxiety Sensitivity Index, a measure of panic-related anxiety. RESULTS: Patients with IEI scored significantly higher on the Anxiety Sensitivity Index than control subjects did (P <.05). Significantly more patients with IEI (71%) than control subjects (26%) fulfilled panic attack criteria after carbon dioxide (P <.001). Physiologic responses to the challenge were not significantly different between groups. CONCLUSIONS: Results suggest that, similar to patients with PD, patients with IEI display high anxiety sensitivity and in response to carbon dioxide inhalation tend to experience heightened anxiety and panic attacks.

Panic response to sodium lactate infusion in patients with multiple chemical sensitivity syndrome.

BACKGROUND: Many patients who are first seen with what has been called multiple chemical sensitivity syndrome (MCS) experience symptoms suggestive of panic disorder including chest tightness, shortness of breath, palpitations, paresthesias, light-headedness, and mental confusion. Although such patients are often convinced that these symptoms reflect toxic effects of environmental "chemicals," direct evidence of this is lacking. To the contrary, a previous study has shown that some of these individuals exhibit hyperventilation responses on exposure to non-noxious stimuli, and it has been suggested that the resulting hypocarbia accounts for their symptoms. We postulated that some patients with self-identified MCS had an underlying condition similar to panic disorder and would therefore demonstrate similar responses to provocative challenges, such as sodium lactate infusion. METHODS: Patients referred to an allergy and clinical immunology service for evaluation of "chemical sensitivity" were investigated to rule out underlying medical conditions, including asthma, as a cause of their symptoms and were enrolled for study after giving informed consent. After a standardized psychiatric assessment was performed, patients underwent single-blind intravenous infusions of normal saline solution (placebo) and sodium lactate (which reproduces symptoms in individuals with underlying panic disorder). All patients were referred for independent psychiatric assessment. RESULTS: The standardized psychiatric assessment identified four of five patients as meeting DSM III-R diagnostic criteria for panic disorder along with other depressive and/or anxiety-related disorders. All five patients with self-identified chemical sensitivity exhibited a positive symptomatic response to sodium lactate compared with placebo infusion. Independent psychiatric assessment confirmed the diagnosis of panic disorder on the basis of DSM III-R criteria in each of the five patients. CONCLUSION: These results suggest that MCS may have a neurobiologic basis similar, if not identical, to that of panic disorder. We speculate that treatments with demonstrated efficacy in panic disorder may also be of benefit in MCS, and conversely, treatments that reinforce anticipatory anxiety and avoidance behavior in patients with MCS may be detrimental.

Adverse cutaneous reactions associated with fluoxetine strategy for reintroduction of this drug in selected patients.

Four patients treated with fluoxetine alone developed generalized urticaria. One also suffered polyarthritis. These reactions subsided when fluoxetine was stopped. After 6-12 months, because of progressive psychiatric problems, fluoxetine was reintroduced using a desensitization protocol. In each case this was well tolerated, and fluoxetine has been continued without adverse affects for 3-10 months.

Cyclosporine in the treatment of nonmicrobial inflammatory ophthalmic disease.

Eighteen patients with severe, progressive nonmicrobial inflammatory ophthalmic disease (including five with intermediate uveitis, four with sympathetic ophthalmia and three with serpiginous choroiditis) that had not responded to conventional therapy were treated with cyclosporine. Three of the four patients with sympathetic ophthalmia responded quickly and maximally, and the fourth showed partial improvement. One patient, with several corneal graft failures in the right eye, started cyclosporine therapy after undergoing left corneal transplantation; at the last follow-up visit the graft had been clear for almost 3 years. The response was inconsistent in patients with other types of eye disease. In general, the drug was well tolerated; however, two patients stopped treatment because of unpleasant side effects. No serious or irreversible complications developed. The results suggest that cyclosporine therapy is useful in the treatment of sympathetic ophthalmia and in high-risk corneal transplantation.

Generalized allergic reactions during anesthesia.

Twenty-eight adults with a history of a generalized allergic reaction during anesthesia were investigated. The reactions were systemic in 23 adults, urticaria/angioedema in four, and bronchial obstruction in one adult. The study population and an additional 35 subjects with a history of use of thiopental during anesthesia but without reactions were investigated by methods including thiopental skin test, succinylcholine skin test, and IgE RAST for antibodies to thiopental, succinylcholine, or latex. Among the 28 patients with reactions, 17 had positive thiopental skin tests; 14/28 reactors and 1/35 of the control group had an IgE thiopental RAST value greater than 2 SD above the mean for control sera from ragweed-allergic subjects. The one control subject with a positive thiopental RAST also was the only control subject with a positive thiopental skin test. IgE succinylcholine RAST was negative in all 23 reactor sera tested. The IgE latex RAST was strongly positive in one reactor. In conclusion, evidence of allergy, particularly allergy to thiopental as a possible basis for the reactions, was obtained in greater than 50% of the patients who were investigated. No allergy to succinylcholine was found.

Acquired Brown's syndrome associated with hypogammaglobulinemia.

We describe a 10-year-old girl with hypogammaglobulinemia who presented initially with painless progressive diplopia on right upward gaze and associated tenderness in the area of the superior oblique tendon (Brown's syndrome). She was given prednisone (40 mg/day) with gradual improvement of her symptoms. Prednisone was tapered and her symptoms remained unchanged for 10 months. She then experienced rapid deterioration. Prednisone was reinstituted with similar improvement and then therapy was switched to naproxen. She remains with only slight diplopia on extreme upward gaze.

Dopamine receptor sites and states in human brain.

Of the several dopamine-sensitive sites in the brain, the one that most correlates with psychomotor behaviour is the D2 receptor. This receptor has two states. The D2Hi state is characterized by its nM affinity for dopamine. The D2Lo state is typified by its microM affinity for dopamine. Neuroleptics have the same affinity (50 pM for spiperone) for both states. Guanine nucleotides convert most, if not all, of the D2Hi sites into D2Lo sites. Any D2Hi sites which are insensitive to GTP, if such exist, may be separate D4 sites. In addition to the binding of 3H-spiperone being higher in post-mortem schizophrenic brains, the proportions of the D2 receptor in the D2Hi state appear to be less in preliminary data on the schizophrenic brain.