Glenn E. Hunt

Breast cancer survivors’ supportive care needs 2–10 years after diagnosis

Goals of the workA significant proportion of breast cancer patients experience psychosocial morbidity after treatment, although their longer-term outcomes and supportive care service needs have not been comprehensively documented. The aim of this study was to identify longer-term outcomes and supportive care needs in disease-free breast cancer survivors.Materials and methodsOne hundred seventeen patients who had been diagnosed with breast cancer 2–10 years earlier completed questionnaires to assess psychosocial outcomes including supportive care needs, psychological distress, and quality of life (QoL).Main resultsQoL and depression scores were consistent with community rates although anxiety scores were higher. Approximately two thirds of survivors reported at least one unmet need, most frequently concerning existential survivorship issues, thereby highlighting the unique needs of survivors. Years since diagnosis was not correlated with need levels. Survivors classified as clinically anxious reported over three times as many unmet needs and survivors classified as depressed reported over two and a half times as many unmet needs. Positive outcomes were frequently reported.ConclusionsThe findings have direct clinical relevance: irrespective of years since diagnosis, comprehensive and extended supportive care services are required to identify breast cancer survivors in need of supportive care interventions and remediate high levels of anxiety.

Neural Correlates of Cat Odor-Induced Anxiety in Rats: Region-Specific Effects of the Benzodiazepine Midazolam

Cat odor elicits a profound defensive reaction in rats that is reduced by benzodiazepine drugs. The neural correlates of this phenomenon were investigated here using Fos immunohistochemistry. Rats received either midazolam (0.75 mg/kg, s.c.) or vehicle and were exposed to pieces of a collar that had been worn by a domestic cat or an unworn (dummy) collar. Cat odor caused midazolam-sensitive defensive behavioral responses, including avoidance of collar contact, inhibition of grooming, and prolonged rearing. Cat odor exposure induced Fos expression in the posterior accessory olfactory bulb (glomerular, mitral, and granule cell layers), with granule cell layer activation attenuated by midazolam. High basal Fos expression, and some cat odor-associated Fos expression, was evident in the main olfactory bulb (glomerular cell layer), and midazolam exerted a strong inhibitory effect in this region. Midazolam inhibited Fos expression in key limbic regions involved in pheromone transduction (medial amygdala and bed nucleus of the stria terminalis) and defensive behavior (prelimbic cortex, lateral septum, lateral and medial preoptic areas, and dorsal premammillary nucleus). However, midazolam failed to affect cat odor-related Fos expression in a range of key defense-related sites, including the ventromedial hypothalamic nucleus, paraventricular nucleus of the hypothalamus, periaqueductal gray, and cuneiform nucleus. These results indicate that midazolam exerts a region-specific effect on the neural substrates activated by predator odor, with effects in the lateral septum and dorsal premammillary nucleus likely to be of major importance. These findings also suggest the intriguing hypothesis that cat odor is processed by rats as a “pheromone-like” stimulus.

Medication compliance and comorbid substance abuse in schizophrenia: impact on community survival 4 years after a relapse.

This prospective study examined the effect of medication compliance and substance abuse on 4 year outcome in 99 patients following a relapse of schizophrenia. Univariate survival analysis revealed longer community tenure in patients if they were over the age of 35 years, not admitted 2 years prior to the index episode, remained medication compliant and did not abuse substances during the follow-up interval. Comparisons between patients grouped according to medication compliance and current substance abuse indicated that those patients who regularly took their medication but also abused substances were readmitted to hospital sooner (median survival, 10 months) compared to compliant patients who did not use substances (37 months). For noncompliant patients, time to first readmission was shorter for patients with a dual diagnosis (5 months) compared to patients with a singular diagnosis of schizophrenia (10 months). Over the 4 year period, noncompliant patients with a dual diagnosis (n=28) accounted for 57% of all hospital readmissions for the cohort and averaged 1.5 admissions per patient year. These data indicate that much of the benefit that antipsychotic medication has on increasing community survival is reduced by substance abuse. This interval is further reduced in patients who are both substance abusers and noncompliant with medication resulting in a revolving door situation of frequent hospital admissions. Integrated treatment programs which address these issues are likely to reduce the need for hospital readmission in patients with a dual diagnosis.

A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy")

The drug 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has a widely documented ability to increase feelings of love and closeness toward others. The present study investigated whether oxytocin, a neuropeptide involved in affiliative behavior, may play a role in this effect. A moderate (5 mg/kg, i.p.) dose of MDMA increased social interaction in male Wistar rats, primarily by increasing the amount of time rats spent lying adjacent to each other. MDMA (5 mg/kg) activated oxytocin-containing neurons in the supraoptic and paraventricular nuclei of the hypothalamus, as shown by Fos immunohistochemistry. MDMA (5 mg/kg i.p.) also increased plasma oxytocin levels and this effect was prevented by pre-treatment with the 5-HT(1A) antagonist N-[2-[4-(2-methyoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg i.p.). The oxytocin receptor antagonist tocinoic acid (20 microg, i.c.v.) had no effect on social behavior when given alone but significantly attenuated the facilitation of social interaction produced by MDMA (5 mg/kg). The 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline) (8-OH-DPAT, 0.25 mg/kg, i.p.) increased social behavior in a similar way to MDMA and this effect was also significantly attenuated by tocinoic acid. Taken together, these results suggest that oxytocin release, stimulated by MDMA through 5-HT(1A) receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.

Psychosocial Treatments for People with Co-occurring Severe Mental Illnesses and Substance Use Disorders (Dual Diagnosis): A Review of Empirical Evidence

&NA; Considerable research documents the health consequences of psychosis and co‐occurring substance use disorders. Results of randomized controlled trials assessing the effectiveness of psychosocial interventions for persons with dual diagnoses are equivocal but encouraging. Many studies are hampered by small, heterogeneous samples, high attrition rates, short follow‐up periods, and unclear description of treatment components. The treatments available for this group of patients (which can be tailored to individual needs) include motivational interviewing, cognitive‐behavioral therapy, contingency management, relapse prevention, case management, and skills training. Regardless of whether services follow integrated or parallel models, they should be well coordinated, take a team approach, be multidisciplinary, have specialist‐trained personnel (including 24‐hour access), include a range of program types, and provide for long‐term follow‐up. Interventions for substance reduction may need to be further developed and adapted for people with serious mental illnesses. Further quality trials in this area will contribute to the growing body of data of effective interventions.

From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long‐term adverse consequences of drug use?

Addictive drugs can profoundly affect social behaviour both acutely and in the long‐term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the ‘social neuropeptide’ oxytocin and its possible role in acute and long‐term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma‐hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin‐dopamine interaction may also influence the acquisition and expression of drug‐seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long‐term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.

Increased anxiety and impaired memory in rats 3 months after administration of 3,4-methylenedioxymethamphetamine ("ecstasy").

Male Wistar rats were administered either (a) a high dose regime of 3,4-methylenedioxymethamphetamine (MDMA) (4 x 5 mg/kg, i.p. over 4 h on each of 2 consecutive days), (b) a moderate dose regime of MDMA (1 x 5 mg/kg on each of 2 consecutive days), (c) D-amphetamine (4 x 1 mg/kg over 4 h on each of 2 days), or (d) vehicle injections. The high MDMA dose regime and the amphetamine treatment both produced acute hyperactivity and hyperthermia. Twelve weeks later, all rats were tested in the drug-free state on a battery of anxiety tests (elevated plus maze, emergence and social interaction tests). A further 2 weeks later they were tested on a novel object recognition memory task. Rats previously given the neurotoxic dose of MDMA showed greater anxiety-like behaviour on all three anxiety tests relative to both controls and D-amphetamine-treated rats. Rats given the moderate MDMA dose regime also showed increased anxiety-like behaviour on all three tests, although to a lesser extent than rats in the high dose group. In the object recognition task, rats given the high MDMA dose regime showed impaired memory relative to all other groups when tested at a 15-min delay but not at a 60-min delay. Rats previously exposed to amphetamine did not differ from saline controls in the anxiety or memory tests. These data suggest that moderate to heavy MDMA exposure over 48 h may lead to increased anxiety and memory impairment 3 months later, possibly through a neurotoxic effect on brain serotonin systems.

Prevalence of comorbid substance use, anxiety and mood disorders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis

BACKGROUND Comorbidity is highly prevalent between substance use disorders (SUDs), mood and anxiety disorders. We conducted a systematic review and meta-analysis to determine the strength of association between SUDs, mood and anxiety disorders in population-based epidemiological surveys. METHODS A comprehensive literature search of Medline, EMBASE, CINAHL, PsychINFO, Web of Science, and Scopus was conducted from 1990 to 2014. Sources were chosen on the basis that they contained original research in non-clinical populations conducted in randomly selected adults living within defined boundaries. Prevalence of comorbid SUDs, mood and anxiety disorders and odds ratios (ORs) were extracted. RESULTS There were 115 articles identified by electronic searches that were reviewed in full text which yielded 22 unique epidemiological surveys to extract lifetime and 12-month prevalence data for psychiatric illness in respondents with an SUD. Meta-analysis indicated the strongest associations were between illicit drug use disorder and major depression (pooled OR 3.80, 95% CI 3.02-4.78), followed by illicit drug use and any anxiety disorder (OR 2.91, 95% CI 2.58-3.28), alcohol use disorders and major depression (OR 2.42, 95% CI 2.22-2.64) and alcohol use disorders and any anxiety disorder (OR 2.11, 95% CI 2.03-2.19). ORs for dependence were higher than those for abuse irrespective to diagnoses based on lifetime or 12-month prevalence. CONCLUSIONS This review confirms the strong association between SUDs, mood and anxiety disorders. The issue has now been recognised worldwide as a factor that affects the profile, course, patterns, severity and outcomes of these disorders.

Increased anxiety 3 months after brief exposure to MDMA ("Ecstasy") in rats: association with altered 5-HT transporter and receptor density.

Male Wistar rats were treated with 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) using either a high dose (4 × 5 mg/kg over 4 h) or low dose (1 × 5 mg/kg over 4 h) regimen on each of 2 consecutive days. After 10 weeks, rats were tested in the social interaction and emergence tests of anxiety. Rats previously given either of the MDMA dose regimens were significantly more anxious on both tests. After behavioral testing, and 3 months after the MDMA treatment, the rats were killed and their brains examined. Rats given the high-, but not the low-, dose MDMA treatment regimen exhibited significant loss of 5-hydroxytryptamine (5-HT) and 5-HIAA in the amygdala, hippocampus, striatum, and cortex. Quantitative autoradiography showed loss of SERT binding in cortical, hippocampal, thalamic, and hypothalamic sites with the high-dose MDMA regime, while low-dose MDMA only produced significant loss in the medial hypothalamus. Neither high- nor low-dose MDMA affected 5HT1A receptor density. High-dose MDMA increased 5HT1B receptor density in the nucleus accumbens and lateral septum but decreased binding in the globus pallidus, insular cortex and medial thalamus. Low-dose MDMA decreased 5HT1B receptor density in the hippocampus, globus pallidus, and medial thalamus. High-dose MDMA caused dramatic decreases in cortical, striatal, thalamic, and hypothalamic 5HT2A/2C receptor density, while low-dose MDMA tended to produce similar effects but only significantly in the piriform cortex. These data suggest that even brief, relatively low-dose MDMA exposure can produce significant, long-term changes in 5-HT receptor and transporter function and associated emotional behavior. Interestingly, long-term 5-HT depletion may not be necessary to produce lasting effects on anxiety-like behavior after low-dose MDMA.

Dexamethasone suppresion test (DST) and plasma dexamethasone levels in depressed patients

The dexamethasone suppression test (DST) was evaluated in newly hospitalized patients with a DSM-III diagnosis of major depression. Patients with other psychiatric disorders and a normal control group were also studied. Plasma dexamethasone levels were obtained in all patients, and the relationship between plasma cortisol and plasma dexamethasone was examined. Rates of non-suppression in patients with major depression (39%) were not significantly different from those in patients with minor depression (25%), mania (38%), or other psychiatric illnesses (17%). The ranges of dexamethasone levels at 8 a.m. and 4 p.m. were similar between patient groups and controls. However, there was a significant difference in dexamethasone levels between suppressors and nonsuppressors, irrespective of diagnosis, which could not be explained by differences in weight or plasma dexamethasone half-life. Inappropriately high dexamethasone levels were found in some patients with a 1 mg test, a problem that critically affects the sensitivity of the test procedure.