Gender differences in schizophrenia have been extensively researched and it is being increasingly accepted that gonadal steroids are strongly attributed to this phenomenon. Of the various hormones implicated, the estrogen hypothesis has been the most widely researched one and it postulates that estrogen exerts a protective effect by buffering females against the development and severity of the illness. In this review, we comprehensively analyse studies that have investigated the effects of estrogen, in particular 17β-estradiol, in clinical, animal, and molecular research with relevance to schizophrenia. Specifically, we discuss the current evidence on estrogen dysfunction in schizophrenia patients and review the clinical findings on the use of estradiol as an adjunctive treatment in schizophrenia patients. Preclinical research that has used animal models and molecular probes to investigate estradiol’s underlying protective mechanisms is also substantially discussed, with particular focus on estradiol’s impact on the major neurotransmitter systems implicated in schizophrenia, namely, the dopamine, serotonin, and glutamate systems.

Intimate partner violence (IPV) may be a major concern in military and veteran populations, and the aims of this systematic review were to (1) provide best available estimates of overall prevalence based on studies that are most representative of relevant populations, and (2) contextualise these via examination of IPV types, impacts, and context. An electronic search of PsycINFO, CINHAL, PubMed, and the Cochrane Library databases identified studies utilising population-based designs or population screening strategies to estimate prevalence of IPV perpetration or victimisation reported by active duty (AD) military personnel or veterans. Random effects meta-analyses were used for quantitative analyses and were supplemented by narrative syntheses of heterogeneous data. Thirty-one studies involving 172,790 participants were included in meta-analyses. These indicated around 13% of all AD personnel and veterans reported any recent IPV perpetration, and around 21% reported any recent victimisation. There were higher rates of IPV perpetration in studies of veterans and health service settings, but no discernible differences were found according to gender, era of service, or country of origin. Psychological IPV was the most common form identified, while there were few studies of IPV impacts, or coercive and controlling behaviours. The findings demonstrate that IPV perpetration and victimisation occur commonly among AD personnel and veterans and highlight a strong need for responses across military and veteran-specific settings. However, there are gaps in understanding of impacts and context for IPV, including coercive and controlling behaviours, which are priority considerations for future research and policy.

Post-traumatic stress disorder (PTSD) is a severe and debilitating condition affecting a significant proportion of the veteran community. A substantial number of veterans with PTSD fail to benefit from trauma-focused psychological therapies or pharmacotherapy or are left with residual symptoms, and therefore, investigation of new and innovative treatment is required. Theta Burst Stimulation (TBS) is a novel form of Repetitive Transcranial Magnetic Stimulation, which has been shown to improve depression symptoms and associated cognitive deficits. The current pilot study aimed to explore the acceptability, safety, and tolerability of intermittent TBS (iTBS) as a treatment for PTSD in Australian veterans. This study employed a case series, repeated-measures design. Eight Australian Defence Force veterans with PTSD received 20 bilateral iTBS treatments (1 session per day, 5 days per week over a 4-week period) and were assessed on a range of mental health and neuropsychological measures, including the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and Hamilton Depression Rating Scale (HAM-D), at pretreatment, post-treatment, and a 3-month follow-up. Treatment was generally welltolerated, with reported side-effects including mild to moderate site-specific cranial pain and headaches during stimulation, which were relieved with the use of low dose analgesics. No serious side effects or adverse events were reported. Participants exhibited reductions in both PTSD and depression symptom severity (the repeated-measures effect size [d_RM] for the CAPS-5 was −1.78, and the HAM-D was −1.16 post-treatment), as well as improvements in working memory and processing speed. Although significance cannot be inferred, these preliminary estimates of effect size indicate change over time. Bilateral iTBS appears to be welltolerated by Australian veterans. Within this repeated-measures case series, iTBS treatment shows promise in reducing both PTSD and mood symptoms, as well as improving cognitive difficulties associated with these disorders. Large-scale randomized controlled trials of this promising treatment are warranted.

17β-estradiol treatment has shown benefit against schizophrenia symptoms, however long-term use may be associated with negative side-effects. Selective estrogen receptor modulators, such as raloxifene and tamoxifen, have been proposed as suitable alternatives to 17β-estradiol. An isomer of 17β-estradiol, 17α-estradiol, is considered less carcinogenic, and non-feminising in males, however little is known about its potential as a treatment for schizophrenia. Moreover, the mechanism underlying the therapeutic action of estrogens remains unclear. We aimed to investigate the ability of these estrogenic compounds to attenuate psychosis-like behaviour in rats. We used two acute pharmacologically-induced assays of psychosis-like behaviour: psychotomimetic drug-induced hyperlocomotion and disruption of prepulse inhibition (PPI). Female Long Evans rats were either intact, ovariectomised (OVX), or OVX and chronically treated with 17β-estradiol, 17α-estradiol, raloxifene or tamoxifen. Only 17β-estradiol treatment attenuated locomotor hyperactivity induced by the indirect dopamine receptor agonist, methamphetamine. 17β-estradiol- and tamoxifen-treated rats showed attenuated methamphetamine- and apomorphine (dopamine D1/D2 receptor agonist)-induced disruption of PPI. Raloxifene-treated rats showed attenuated apomorphine-induced PPI disruption only. Baseline PPI was significantly reduced following OVX, and this deficit was reversed by all estrogenic compounds. Further, PPI in OVX rats was increased following administration of apomorphine. This study confirms a protective effect of 17β-estradiol in two established animal models of psychosis, while tamoxifen showed beneficial effects against PPI disruption. In contrast, 17α-estradiol and raloxifene showed little effect on dopamine receptor-mediated psychosis-like behaviours. This study highlights the utility of some estrogenic compounds to attenuate psychosis-like behaviour in rats, supporting the notion that estrogens have therapeutic potential for psychotic disorders.