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The influence of substance use on patient's needs and caregiving consequences has received insufficient research attention. We sought to determine whether patients with comorbid substance use have higher levels of need, anxiety, depression, and caregiving consequences than those of patients who do not use substances. A total of 520 patients participated, and those who used substances (n = 216) reported higher levels of unmet needs, anxiety, and caregiving consequences than did patients who did not use substances. Carers of patients who used substances also reported higher anxiety and more caregiving consequences. Very few patients were actively involved in treatment programs to reduce their substance use.

In recent work we have documented lasting adverse neurochemical and behavioural effects in rats given short-term 'binge' dosing with methylenedioxymethamphetamine (MDMA, Ecstasy), methamphetamine (METH) or their combination. Here we investigated whether similar effects persist in rats given 16 weekly injections followed by a 10 week period of abstinence. Female rats received MDMA (8 mg/kg, i.p.), METH (8 mg/kg), or a MDMA/METH combination (4 mg/kg MDMA + 4 mg/kg METH), once a week for 16 weeks, with locomotor activity and body temperature measured on weeks 1, 8 and 16. The MDMA and MDMA/METH groups showed acute drug-induced hyperthermia on week 1 only. MDMA-treated rats demonstrated an acute hyperactivity while METH and MDMA/METH treated rats showed pronounced stereotypy. Seven weeks after drug-treatment concluded, a decrease in social interaction was observed in all chronically drug-treated rats. No group differences were evident on the emergence, object recognition or forced swim tests. Neurochemical analysis revealed modest noradrenaline and serotonin depletion in chronically treated rats that was not evident following a single equivalent administration. These results indicate that although chronic, intermittent exposure to MDMA, METH or their combination, may not lead to significant long-term monoamine depletion, lasting adverse behavioural effects may persist, especially those related to social behaviour.

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.

Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 x 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.

Rationale: There is some uncertainty whether the acute hyperthermia caused by MDMA (ecstasy) plays a significant role in determining the long-term neurotoxic effects on brain 5-HT systems and associated changes in mood and behaviour., Objective: The present study assessed whether long-term behavioural and cognitive changes seen in MDMA-treated rats are affected by hyperthermia at the time of drug administration., Method: Male Wistar rats were treated with MDMA (4x5 mg/kg i.p. over 4 h on 2 consecutive days) or vehicle at either a high ambient temperature (28 degrees C) or a low ambient temperature (16 degrees C). Eight to 18 weeks later, rats were tested in behavioural measures of anxiety (social interaction and emergence tests), a test of cognition (object recognition test) and the forced swim test of depression. At the conclusion of behavioural testing the rats were killed and their brains analysed using HPLC., Results: MDMA treatment caused a clear and consistent hyperthermia at 28 degrees C and hypothermia at 16 degrees C. Months later, rats pre-treated with MDMA at either 16 or 28 degrees C displayed increased anxiety in the social interaction and emergence tests and reduced escape attempts and increased immobility in the forced swim test. MDMA pre-treatment was also associated with poorer memory on the object recognition test, but only in rats given the drug at 28 degrees C. Rats pre-treated with MDMA showed loss of 5-HT in the hippocampus, striatum, amygdala and cortex, regardless of body temperature at the time of dosing. However, 5-HIAA loss in the amygdala and hippocampus was greater in rats pre-treated at 28 degrees C. Dopamine in the striatum was also depleted in rats given MDMA., Conclusions: These results indicate that hyperthermia at the time of dosing with MDMA is not necessary to produce subsequent 5-HT depletion and anxiety in rats. They also extend previous findings of long-term effects of brief exposure to MDMA in rats to include apparent "depressive" symptoms in the forced swim model.

Male Wistar rats were treated with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") using either a high dose (4 x 5 mg/kg over 4 h) or low dose (1 x 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 5HT(1A) receptor density. High-dose MDMA increased 5HT(1B) 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 5HT(1B) receptor density in the hippocampus, globus pallidus, and medial thalamus. High-dose MDMA caused dramatic decreases in cortical, striatal, thalamic, and hypothalamic 5HT(2A)/(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.

The long-term behavioural and neurotoxic effects of 3,4-methlyenedioxymethampthetamine (MDMA, "Ecstasy") were examined in rats. Rats were given MDMA (5 mg/kg i.p. once per hour for 4 h) or vehicle injections on each of two consecutive days at an ambient temparature of 28 degrees C. MDMA caused acute hyperthermia and locomotor hyperactivity on both days. Four and six weeks after drug administration the rats previously treated with MDMA showed elevated levels of anxiety-like behaviour in the emergence and social interaction tests, respectively. At 9 weeks post-MDMA, the rats displayed an increase in anxiety on the elevated plus-maze test relative to controls. Ten weeks following treatment the rats were killed and their brains dissected and neurotramitter content analysed using High Performance Liquid Chromotography (HPLC). Rats previously given MDMA showed significantly decreased 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the amygdala, hippocampus and striatum relative to controls. This 5-HT depletion may have a causal role in producing increased anxiety-like behaviours in MDMA-treated rats. These results are consistent with human studies suggesting that exposure to high doses of MDMA may predispose to long-term psychological problems such as anxiety and depression.

Autism spectrum conditions are a group of neurodevelopmental conditions that carries an array of co-occurring diagnoses, including a heightened risk of suicide attempts and suicide. This scoping review examined primary research focusing on autism and suicidality, to understand what is currently known on the topic, including how autism changes the presentation of suicidal thoughts and behavior; and to assess the suicide awareness and prevention education programs currently available for autistic people, their families, and health professionals and support workers. A comprehensive search (November 2021) across Scopus, PubMed and CINAHL identified 39 articles from 38 studies. Three themes emerged, with five subthemes. 1. The prevalence of suicidality in autistic people; 2. The presentation of suicidality in autistic people, including (a) risk of suicidality; (b) gender, age, employment and education; (c) co-occurring psychiatric conditions; (d) autism traits and social communication; (e) intellectual disability; and 3. Autism-specific approaches to suicidal thoughts, behavior and prevention. Findings were mixed, including conflicting evidence on the risk of autism and suicidality, and limited evidence of resources related to autism-specific suicide awareness or information, and education or prevention programs. [ABSTRACT FROM AUTHOR]

Abstract: Comparisons were made between young (3–6 months) and aged (20–30 months) Wistar rats on locomotor activity, emergence, social interaction and cat odor avoidance. Aged rats were less active and spent less time in the open field during the emergence test than younger rats. Older rats also showed fewer contacts with a novel conspecific in the social interaction test, although total duration of interaction did not differ. There were very few behavioral differences between male and female rats. Older rats were less reactive than younger rats in a test of cat odor avoidance. However, they expressed similar amounts of cat odor-induced Fos in the posterior accessory olfactory bulb, a critical region for processing the predator odor stimulus. Older rats had reduced Fos expression in several defense-related brain regions that are normally activated by predator odors such as the medial amygdala and dorsal premammillary nucleus. These results indicate that aged rats are less reactive than younger rats to predator odors due to decreased responsiveness in defense-related but not necessarily olfactory circuits. [Copyright &y& Elsevier]

Background Nutritional rehabilitation in anorexia nervosa (AN) is impeded by fear of food, eating and change leading to treatment resistance. Oxytocin (OT) exerts prosocial effects and modulates trust, fear, anxiety and neuroplasticity. The current placebo-controlled RCT examined the effects of intranasal oxytocin (IN-OT) in AN. The aim was to ascertain whether repeated doses of IN-OT enhance treatment outcomes in AN. Methods AN patients self-administered 36 IU IN-OT or placebo daily for 4–6 weeks during hospital treatment. The outcome measures were change in the Eating Disorders Examination (EDE) scale, weight gain, cognitive rigidity, social anxiety, obsessive and autistic symptoms. The effects of the first and last doses of IN-OT were assessed relative to placebo before and after a high-energy afternoon snack, to determine potential dampening of cortisol and anxiety levels by OT. Results Weight gain was similar in both groups. The EDE eating concern subscale score was significantly lower after IN-OT treatment as was cognitive rigidity. There were no significant differences in social anxiety or any of the other outcomes at follow-up. After four weeks IN-OT, salivary cortisol levels were significantly lowered in anticipation of an afternoon snack compared to placebo. Morning plasma OT levels did not change after chronic IN-OT or with weight restoration. Conclusion IN-OT might enhance nutritional rehabilitation in AN by reducing eating concern and cognitive rigidity. Lower salivary cortisol levels in response to IN-OT suggest diminished neuroendocrine stress responsiveness to food and eating. Such effects require replication with inclusion of more sensitive subjective measures. [ABSTRACT FROM AUTHOR]

Abstract: The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4×5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT1A agonist 8-OH-DPAT (250 µg/kg but not 125 µg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT1A receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]