Associations between goal orientation and suicidal thoughts and behaviors at one-month follow-up: Indirect effects through ruminative flooding.

Previous research has identified both goal orientation and ruminative flooding as potential risk factors for suicidal thoughts and behaviors, as well as positive associations between goal orientation and rumination. The present study examined whether the association between goal orientation and suicidal thoughts and behaviors, assessed one month later, was accounted for by ruminative flooding. A sample of 924 psychiatric outpatients (Mage = 39.09 years, SD = 14.82, range = 18 to 84; 61.7% female; 37.0% White) completed self-report and interview measures at baseline and provided information about suicide-related outcomes at one-month follow-up. Goal orientation was positively associated with ruminative flooding, and both goal orientation and ruminative flooding were associated with suicidal thoughts and behaviors at one-month follow-up. Controlling for lifetime suicidal thoughts and behaviors, as well as patient age and sexual orientation, ruminative flooding accounted for the relationship between goal orientation and suicidal thoughts and behaviors at one-month follow-up. These findings were especially relevant for individuals with a history of multiple suicide attempts. Overall, this study provided evidence that difficulties with goal orientation may relate to suicidal thoughts and behaviors through intense ruminations perceived as a loss of cognitive control. Interventions that address ruminative thinking and cognitive flexibility may, in turn, assist in reducing emotion dysregulation and managing suicidality among those who struggle with goal orientation.

Perfectionism and Prospective Near-Term Suicidal Thoughts and Behaviors: The Mediation of Fear of Humiliation and Suicide Crisis Syndrome.

BACKGROUND: Perfectionism has been linked to suicide. According to the Narrative-Crisis Model of suicide, individuals with trait vulnerabilities are prone to develop a certain mindset, known as a Suicidal Narrative, which may precipitate the Suicide Crisis Syndrome (SCS), culminating in suicide. The purpose of this study was to investigate the association between perfectionism (trait vulnerability), fear of humiliation (component of the Suicidal Narrative), SCS, and prospective near-term suicidal thoughts and behaviors (STB). METHODS: Adult psychiatric outpatient participants (N = 336) were assessed at baseline with the Suicidal Narrative Inventory for perfectionism and fear of humiliation. The questions used to assess perfectionism were adapted from the Multidimensional Perfectionism Scale. The severity of the SCS was calculated using the Suicide Crisis Inventory. STB were assessed at baseline and after one month using the Columbia Suicide Severity Rating Scale. Serial mediation analyses were conducted using PROCESS version 3.3 in SPSS. RESULTS: While the direct effect of perfectionism on prospective STB was not significant (b = 0.01, p = 0.19), the indirect effect of perfectionism on STB, through serial mediation by fear of humiliation and the SCS, was significant (indirect effect p = 0.007, 95% CI [0.003,0.013]). The indirect effect was not significant for models that did not include both mediators. LIMITATIONS: Variables were assessed at one time only. CONCLUSION: Perfectionism did not directly modulate STB. Perfectionism may be related to suicidal behavior through fear of humiliation, leading to the SCS. These results support the Narrative-Crisis Model of suicide and clarify the role of perfectionism in the etiology of suicide.

Themes and trends in intentional self-poisoning: Perspectives from critical care toxicology.

This research investigated the substances employed by and experiences of patients who come to acute treatment after self-poisoning. A retrospective search of the Toxicology Investigators Consortium Registry was performed to characterize a large cohort of patients. A detailed prospective study of one inpatient toxicology service was also conducted. Patients chose readily available agents for self-poisoning. Most cases involved at least one substance that affects the central nervous system (CNS). The majority were prescription psychotropics and narcotics. When they had access to both CNS-active and CNS-inactive medications, patients almost invariably ingested a mind-altering agent. After recovering neurocognitive function, most patients were not actively experiencing suicidal thoughts. However, more than half of patients without CNS toxicity continued to have suicidal ideation after coming to care. These findings are consistent with the hypothesis that many suicidal patients may be seeking an altered psychosomatic state rather than death per se.

Assessment and Management of Toxidromes in the Critical Care Unit.

The most important diagnostic factor in uncovering a toxic etiology for delirium or critical illness is the clinician's openness to the possibility of its existence. Therefore, a consulting psychiatrist, already prepared to perform the detail-oriented work of sorting out behavioral manifestations of disease, can be a vital asset at the bedside if also attuned to the role of purposeful, accidental, and iatrogenic exposures in the intensive care unit. This article summarizes the presentation, evaluation, and treatment of toxidromes relevant to the work of acute psychosomatic medicine.

Mutations in KIAA0753 cause Joubert syndrome associated with growth hormone deficiency.

Joubert syndrome and related disorders (JSRD) are a heterogeneous group of ciliopathies defined based on the mid-hindbrain abnormalities that result in the characteristic "molar tooth sign" on brain imaging. The core clinical findings of JSRD are hypotonia, developmental delay, abnormal eye movements and breathing abnormalities. To date, more than 30 JSRD genes that encode proteins important for structure and/or function of cilia have been identified. Here, we present 2 siblings with Joubert syndrome associated with growth hormone deficiency. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). The intronic mutation alters normal splicing by activating a cryptic acceptor splice site in exon 16. The novel acceptor site skips nine nucleotides, deleting three amino acids from the protein coding frame. KIAA0753 (OFIP) is a centrosome and pericentriolar satellite protein, previously not known to cause Joubert syndrome. We present comprehensive clinical descriptions of the Joubert syndrome patients as well as the cellular phenotype of defective ciliogenesis in the patients' fibroblasts.

The effect of ratio and interval training on Pavlovian-instrumental transfer in mice.

Conditional stimuli (CS) that are paired with reward can be used to motivate instrumental responses. This process is called Pavlovian-instrumental transfer (PIT). A recent study in rats suggested that habitual responses are particularly sensitive to the motivational effects of reward cues. The current experiments examined this idea using ratio and interval training in mice. Two groups of animals were trained to lever press for food pellets that were delivered on random ratio or random interval schedules. Devaluation tests revealed that interval training led to habitual responding while ratio training produced goal-directed actions. The presentation of CSs paired with reward led to positive transfer in both groups, however, the size of this effect was much larger in mice that were trained on interval schedules. This result suggests that habitual responses are more sensitive to the motivational influence of reward cues than goal-directed actions. The implications for neurobiological models of motivation and drug seeking behaviors are discussed.

mGluR5 receptors in the basolateral amygdala and nucleus accumbens regulate cue-induced reinstatement of ethanol-seeking behavior.

Pharmacological blockade of the type 5 metabotropic glutamate receptor (mGluR5) attenuates cue-induced reinstatement of ethanol-seeking behavior, yet the brain regions involved in these effects are not yet known. The purpose of the present study was to determine if local blockade of mGluR5 receptors in the basolateral amygdala (BLA) and/or the nucleus accumbens (NAc), two brain regions known to be involved in stimulus-reward associations, attenuate the reinstatement of ethanol-seeking behavior induced by ethanol-paired cues. As a control for possible non-specific effects, the effects of mGluR5 blockade in these regions on cue-induced reinstatement of sucrose-seeking were also assessed. Male Wistar rats were implanted with bilateral microinjection cannulae aimed at the BLA or NAc. Following recovery, animals were trained to self-administer ethanol (10% w/v) or 45 mg sucrose pellets on an FR1 schedule of reinforcement in 30 min daily sessions using a sucrose fading procedure. Following stabilization of responding, animals underwent extinction training. Next, animals received infusions of vehicle or the selective mGluR5 antagonist MTEP (3 µg/µl) into the BLA or NAc prior to cue-induced reinstatement testing sessions. mGluR5 blockade eliminated cue-induced reinstatement of alcohol - but not sucrose-seeking behavior. Results from this study indicate that mGluR5 receptors in the BLA and NAc mediate cue-induced reinstatement of ethanol-seeking behavior, and provide two potential neuroanatomical sites of action where systemically administered mGluR5 antagonists attenuate cue-induced reinstatement. These data are consistent with previous findings that cue-induced reinstatement of ethanol-seeking increases neuronal activity and glutamatergic transmission in these two regions.

Alcohol-seeking behavior is associated with increased glutamate transmission in basolateral amygdala and nucleus accumbens as measured by glutamate-oxidase-coated biosensors.

Relapse is one of the most problematic aspects in the treatment of alcoholism and is often triggered by alcohol-associated environmental cues. Evidence indicates that glutamate neurotransmission plays a critical role in cue-induced relapse-like behavior, as inhibition of glutamate neurotransmission can prevent reinstatement of alcohol-seeking behavior. However, few studies have examined specific changes in extracellular glutamate levels in discrete brain regions produced by exposure to alcohol-associated cues. The purpose of this study was to use glutamate oxidase (GluOx)-coated biosensors to monitor changes in extracellular glutamate in specific brain regions during cue-induced reinstatement of alcohol-seeking behavior. Male Wistar rats were implanted with indwelling jugular vein catheters and intracerebral guide cannula aimed at the basolateral amygdala (BLA) or nucleus accumbens (NAc) core, and then trained to self-administer alcohol intravenously. A separate group of animals were trained to self-administer food pellets. Each reinforcer was accompanied by the presentation of a light/tone stimulus. Following stabilization of responding for alcohol or food reinforcement, and subsequent extinction training, animals were implanted with pre-calibrated biosensors and then underwent a 1-hour cue-induced reinstatement testing period. As determined by GluOx-coated biosensors, extracellular levels of glutamate were increased in the BLA and NAc core during cue-induced reinstatement of alcohol-seeking behavior. The cumulative change in extracellular glutamate in both regions was significantly greater for cue-induced reinstatement of alcohol-seeking behavior versus that of food-seeking behavior. These results indicate that increases in glutamate transmission in the BLA and NAc core may be a neurochemical substrate of cue-evoked alcohol-seeking behavior.