Critical review of the categorical structures of the core Conflictual Relationship Theme Method (CCRT)

The CCRT-method developed by Lester Luborsky is the most widespread and best established method to assess relationship structures in the field of psychodynamic psychotherapy research. Although its categorical structures are criticised in many different ways there have not been any attempts to modify them. This article points out the inconsistency of the current categorical system and demonstrates first approaches to alternative solutions. For this purpose genetic algorithms are used. Their application in psychotherapy research is demonstrated here for the first time.     

Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats

Systemic administration of dopamine (DA) agonists markedly disrupts sensorimotor gating in rats as measured by prepulse inhibition (PPI) of the acoustic startle response. A qualitatively similar, but quantitatively weaker disruption of PPI follows DA infusion into the nucleus accumbens (NAC). The present study was designed to determine whether forebrain DA terminal fields other than the NAC contribute to the DAergic modulation of PPI. PPI was impaired significantly after infusion of DA (0–40 µg) into the NAC or anteromedial striatum, but not after DA infusion into the orbital cortex or posterolateral striatum. DA infusion into the amygdala also disrupted PPI, but this disruption was accompanied by a dose-dependent decrease in startle amplitude. These results suggest that DA overactivity in the both NAC and anteromedial striatum contribute to the gating-disruptive effects of systemically administered DA agonists, and that DA overactivity in mesocortical, mesoamygdaloid and non-limbic mesostriatal DA systems are not major substrates for a DAergic modulation of PPI.     

The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications

The startle reflex is a contraction of the skeletal and facial musculature in response to an intense sensory stimulus. While the 'primary' neural control of startle involves brain structures at, or below, the level of the mesencephalon, the startle reflex (SR) exhibits several forms of plasticity that are modulated by the forebrain. Sensorimotor gating of the SR occurs when the reflex is inhibited by a weak 'pre-pulse' that occurs 30-500 ms prior to the startling stimulus. Since 'pre-pulse inhibition' (PPI) of startle may be impaired in certain psychiatric and neurologic disorders (e.g. schizophrenia, schizotypal personality disorder and Huntington's disease), there has been considerable interest in determining the neural substrates of this form of startle plasticity. In rats, PPI is modulated by neural elements linking the limbic cortex with the striatum and pallidum. These substrates may include hippocampal glutamate efferents to the ventral striatum and striatal GABAergic efferents to the ventral pallidum. The striatal dopaminergic modulation of PPI appears to involve primarily D2, but not D1, receptors. Pallidal efferents may impinge directly on the 'primary' startle circuitry via projections to the mesencephalon or, indirectly, via projections to the thalamus. Evidence is reviewed for other neurochemical substrates of PPI-including acetylcholine and opiates. Sensorimotor gating of the startle reflex appears to have a discrete and identifiable set of neural substrates that may be important for our understanding of neuropsychiatric disorders characterized by deficient suppression or 'gating' of sensory, cognitive or motor processes.     

LSD-induced alterations of locomotor patterns and exploration in rats

A free exploration test was used to examine the effects of LSD on investigatory responding and locomotor activity in a novel environment. Rats were injected with 20–30 g/kg LSD or saline prior to being placed in a home cage. After 10 min, a door was opened permitting entry into a larger holeboard chamber where crossovers, rearings, hole pokes, and routes of locomotion were monitored. When administered either 10 or 30 min prior to testing, LSD reduced the time spent in the holeboard chamber only during the first half of a 1-h session, resulting in a corresponding reduction in all holeboard activity measures. In the subsequent 30 min, LSD-treated rats maintained a steady level of responding, in contrast to the continual derement exhibited by controls. Despite their initial avoidance of the holeboard, LSD-treated rats made consistently longer hole pokes into floor holes and showed a more diversified pattern of locomotion than did controls throughout the 1-h session. Most striking was the failure of LSD-treated rats to establish the stereotyped excursion routes, characteristic of controls, from the home cage to various parts of the holeboard. It is suggested that LSD potentiates both neophobic (avoidance) and investigatory responses to a novel environment by retarding the rate of behavioral habituation.     

LSD-induced alterations of investigatory responding in rats

The effects of lysergic acid diethylamide (LSD) on investigatory responses of rats in a novel hole-board were assessed in a series of experiments. LSD (40–160 g/kg) altered the temporal distribution of nose-poke responses during a 24-min session; LSD-treated rats responded less than controls initially, yet increased their response rates late in the session. This dose-dependent effect was not related to the time course of the drug's action nor to alterations in general locomotor activity. Only partial tolerance was found after eight daily injections of 100 g/kg LSD. When handling stress was minimized by placing the animals in an anteroom for 10 min before starting the test, the distribution of responding was normal although the overall frequency was still reduced. Conversely, vigorous handling potentiated the LSD effect. These results are interpreted as indicating an increased sensitivity of the LSD-treated rats to the stimuli associated with being handled and placed into the novel hole-board rather than a direct effect on investigatory tendencies. This LSD-induced potentiation of defensive responses appears to compete with the active exploration of the novel environment.R. K. Light is presently at the Department of Psychology, Indiana University, Bloomington, Indiana.     

Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications

OBJECTIVE: Patients with schizophrenia have deficits in attention, cognition, and information processing. Measures such as P50 suppression are used to study cognitive and attentional dysfunction among these patients. P50 suppression is an operational measure of sensory gating that can be assessed by averaging electroencephalographic responses to multiple pairs of auditory clicks separated by 500 msec. Normally, the P50 response to the second click is smaller than the response to the first click. Many studies have demonstrated that schizophrenia patients have deficient P50 suppression, meaning that the difference between the first and second clicks is not as large as normal. Atypical antipsychotic medications may have superior clinical efficacy for negative symptoms and cognitive deficits. It is important, therefore, to evaluate the effects of atypical antipsychotic medications on measures such as P50 suppression. METHOD: P50 suppression of 13 patients with schizophrenia receiving clinically effective doses of clozapine, olanzapine, or risperidone (classified as atypical antipsychotic medications) was compared to that of 13 patients receiving conventional antipsychotic medications. RESULTS: The patient groups did not differ on clinical or demographic measures. The patients receiving atypical antipsychotic medications had normal-range P50 suppression (mean=72%). In contrast, the patients receiving typical antipsychotic medications had dramatically lower P50 suppression (mean=27%). CONCLUSIONS: The results support the hypothesis that patients treated with atypical antipsychotic medications have normal P50 measures of sensory gating. Longitudinal within-subjects studies are warranted to clarify the mechanisms mediating this effect.     

Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31.

PURPOSE: Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) -positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. PATIENTS AND METHODS: National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. RESULTS: Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for > or = 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. CONCLUSION: Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy.     

The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice.

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.     

The additive miotic effects of dapiprazole and pilocarpine

Background: Since dapiprazole on alpha-adrenergic agent, produces miosis by paralyzing the dilator muscle, and pilocarpine, a parasympathetic drug, causes miosis by affecting the sphincter, we speculated that the two drugs might have additive effects. Methods: The additive miotic actions of pilocarpine 2% and dapiprazole 0.5% were evaluated by comparing the effects of two drugs given together and alone on the reversal of mydriasis induced by tropicamide (0.5%) and phenylephrine (10%) in one eye each of 60 healthy volunteers. Results: Dapiprazole and pilocarpine together induced miosis significantly faster than each drug alone, showing additive effects. Conclusion: Co-administration of dapiprazole and pilocarpine at the end of the eye examination will induce fast pupillary constriction, which might be useful in preventing the development of an acute attack of angle-closure glaucoma in patients with anatomically narrow angles.