"Thinking too much": A systematic review of a common idiom of distress.

Idioms of distress communicate suffering via reference to shared ethnopsychologies, and better understanding of idioms of distress can contribute to effective clinical and public health communication. This systematic review is a qualitative synthesis of "thinking too much" idioms globally, to determine their applicability and variability across cultures. We searched eight databases and retained publications if they included empirical quantitative, qualitative, or mixed-methods research regarding a "thinking too much" idiom and were in English. In total, 138 publications from 1979 to 2014 met inclusion criteria. We examined the descriptive epidemiology, phenomenology, etiology, and course of "thinking too much" idioms and compared them to psychiatric constructs. "Thinking too much" idioms typically reference ruminative, intrusive, and anxious thoughts and result in a range of perceived complications, physical and mental illnesses, or even death. These idioms appear to have variable overlap with common psychiatric constructs, including depression, anxiety, and PTSD. However, "thinking too much" idioms reflect aspects of experience, distress, and social positioning not captured by psychiatric diagnoses and often show wide within-cultural variation, in addition to between-cultural differences. Taken together, these findings suggest that "thinking too much" should not be interpreted as a gloss for psychiatric disorder nor assumed to be a unitary symptom or syndrome within a culture. We suggest five key ways in which engagement with "thinking too much" idioms can improve global mental health research and interventions: it (1) incorporates a key idiom of distress into measurement and screening to improve validity of efforts at identifying those in need of services and tracking treatment outcomes; (2) facilitates exploration of ethnopsychology in order to bolster cultural appropriateness of interventions; (3) strengthens public health communication to encourage engagement in treatment; (4) reduces stigma by enhancing understanding, promoting treatment-seeking, and avoiding unintentionally contributing to stigmatization; and (5) identifies a key locally salient treatment target.

Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann–Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.