Contrary to expert predictions , binge alcohol drinking and recreational drug use declined from pre-pandemic data collection to early-pandemic follow-up.Though we cannot identify specific factors that inform these trends, findings from research with PLHIV suggest a potential association between perceived susceptibility to SARS-CoV-2 acquisition and symptoms and changes in recreational drug use behaviors . The pandemic ushered in widespread fear, anxiety, and uncertainty as no one knew how COVID-19 might increase the risk for SARS-CoV-2 acquisition among PLHIV . Despite these fears and perceptions, investigating the psychosocial and behavioral strengths that influenced the decline of alcohol and recreational drug use behaviors warrants further scrutiny. Alternatively, alcohol and recreational drug use may have decreased because of structural COVID-19 mitigation practices implemented nationwide. Local mandates limited social gatherings and shuttered businesses , practices that may have stymied alcohol and recreational drug use, especially among persons who consume substances primarily within social and sexual contexts . PLHIV’s adherence levels to COVID-19 mitigation efforts, like social distancing, may better inform changes in substance use behaviors. When observing between-group differences, depressive symptoms were consistently associated with each substance use trajectory. These findings are consistent with prior studies . Though researchers have previously linked social support and loneliness to alcohol and substance use behaviors among PLHIV , our analyses yielded inconsistent findings. In bivariate tests, loneliness levels early in the pandemic were positively associated with binge drinking and substance use trajectories. In multi-variable models,vertical farms companies functional social support was inversely associated with membership in the ‘any recreational drug use’ trajectory group, reinforcing the health-promotive qualities of social relationships in PLHIV’s lives .

Our non-significant findings may be attributed to the limited variability of psychosocial factors within our sample. Overall, PLHIV in the MWCCS reported low levels of loneliness and high levels of functional support when the pandemic began. Over 75% reported having two to three people that they can rely on for support. Consistent with prior studies, male sex was positively linked to substance use trajectories, which may reflect sex-related disparities in psychosocial and environmental risk factors . Although we examined group-based trajectories in alcohol, marijuana, and recreational drug use, we did not analyze other consequences of COVID-19, such as changes in livelihood, and the impact of the pandemic on loved ones. Therefore, we cannot pinpoint specific stressors or strengths that shaped our participants’ substance use trajectories. Our results may not apply to other samples of men and women living with HIV. MACS and WIHS participants are part of a longstanding HIV survivor cohort, who are predominantly middle-aged, although the mean age of our sample aligns with the statistic that over half of PLHIV in the United States are above the age of 50 . In prior studies, pre-COVID substance use trajectories in PLHIV have exhibited age-related differences on specific substances consumed ; therefore, cohorts of younger aged individuals may report different COVID-19 substance use patterns. Our sample also represents people who are largely linked to health care, and accustomed to the requirements involved in cohort study participation . Furthermore, the right skew distribution of some of our study’s psychosocial variables may inform inconsistent or different findings observed with more psychosocially diverse samples. Our sample’s low rates of substance use, particularly with recreational drugs, limited our capacity to explore more nuanced ways of looking at group-based trajectories, such as the frequency and specific types of substances that participants used. Furthermore, we were unable to distinguish participants who use marijuana for medical versus recreational purposes; many study sites are in states where HIV seropositivity is an eligible indicator for medical cannabis use. Finally, our study is susceptible to the inherent challenges of conducting survey research, including limitations linked to self-report, subjectivity, social desirability, and the proclivity of participants to under-report behaviors on sensitive topics, like mental health and substance use.

Future studies should investigate the ongoing impact of COVID-19 on the psychosocial well-being of PLHIV. This study examined substance use trajectories only in the short-term. Future MWCCS analyses may improve the precision in identifying substance use trajectories among PLHIV, and to assess the long-term psychosocial consequences of the pandemic beyond the three time points included in our analysis. Because depressive symptoms, loneliness, and social support variables were collected at the start of COVID-19 pandemic efforts , future analyses should examine how changes in cooccurring psychosocial profiles alter PLHIV’s substance use trajectories. Additional studies may benefit from alternative conceptualizations of substance use to inform pandemic-related trajectories . Furthermore, the Centers for Disease Control and Prevention reported that overdose deaths have accelerated during the COVID-19 pandemic . Though our study focuses on substance use frequency, future studies should evaluate how pandemic stressors have impacted the amount of alcohol and drugs PLHIV consumed at times of use. Finally, researchers should implement mixed-methods approaches to better identify health-promotive factors that interrupt problematic trajectories in substance use. The COVID-19 pandemic has emphasized the importance of monitoring and evaluating alcohol and substance use in PLHIV. Since the start of the pandemic, health providers have adapted their service provision to maximize patients’ retention in healthcare . As mitigation recommendations continue to be updated, consistent evaluations of PLHIV’s substance use trajectories amidst the COVID-19 pandemic may better equip health systems to effectively respond to complex and co-occurring challenges as new public health emergencies arise. Furthermore, researchers predicted that mitigation strategies elevated peoples’ risks for adverse conditions, like depression and loneliness. These conditions already disproportionately effect PLHIV and are linked to decreased engagement in HIV care. Yet, we found that binge alcohol consumption and recreational drug use decreased at the beginning of the pandemic among substance-using PLHIV.

Furthermore, depressive symptoms distinguished PLHIV with substance use trajectories from those with non-use trajectories. Ongoing surveillance must continue in order to substantiate our findings, elucidate the COVID-19 pandemic’s complex and co-occurring contributions to psychosocial conditions, and inform the supportive factors that interrupt negative behavioral health trajectories experienced by PLHIV. The exact pathophysiology and aetiology of the severe mental disorders schizophrenia and bipolar disorder remain unknown. They have been hypothesized to be part of the same psychosis continuum, since they in addition to overlapping symptoms share some genetic underpinnings , cognitive impairments and brain anatomical abnormalities . Whereas pre- and perinatal complications have been established as risk factors for schizophrenia , the evidence for an association between pre- and perinatal adversities and the risk for bipolar disorder is less consistent. Some authors have argued that in genetically susceptible individuals, the absence of pre- and perinatal complications favours the development of bipolar disorder whereas their presence favours the development of schizophrenia . Nevertheless, some epidemiological studies suggest that pre- and perinatal factors may increase the risk for bipolar disorder and affective psychosis. Hultman et al. have demonstrated an association between specific obstetric complications and affective psychosis; an increasing birth weight was found to linearly associate with decreased risk for affective disorders ; recently, increased risk for bipolar disorder in children born pre-term [odds ratio 2.7, 95% confidence interval 1.6–4.5] was reported. Accordingly, neurodevelopmental disturbances and/or pre- and perinatal trauma may also be of importance for the development of bipolar disorder. Magnetic resonance imaging studies have demonstrated the existence of neuroanatomical abnormalities in bipolar disorder , the most consistent finding being enlarged ventricular volumes . The results for other brain structures differ among studies, possibly due to low sample sizes and confounding factors,vertical greenhouse farming such as lithium medication. Recent meta-analyses report that lithium-naive patients with bipolar disorder have smaller hippocampal and amygdala volumes as compared with patients who receive lithium medication and with healthy controls . There is also some evidence supporting more pronounced brain abnormalities in patients with psychotic bipolar disorder than in patients with non-psychotic disorder . The mechanisms underlying the structural brain abnormalities observed in bipolar disorder are not completely known. Post-mortem studies have demonstrated reduced neural somal size and neuron numbers in the amygdala, and reduced number of parvalbumin- and somatostatin-expressing interneurons and reduced pyramidal cell size in the hippocampus of bipolar disorder patients. These neuronal changes may have a developmental origin, given the fact that animal models have demonstrated long-term neuronal loss in the amygdala and reduced pyramidal cell size in the hippocampus following pre- and perinatal hypoxia. Moreover, smaller hippocampal volumes and larger ventricular volumes have been demonstrated in schizophrenia patients with a history of pre- and perinatal hypoxia . Enlarged ventricles have also been observed in schizophrenia patients who suffered prolonged birth . In schizophrenia, smaller hippocampal volumes have been reported following OCs in general , and severe OCs have been reported to interact with the hypoxia regulated GRM3 gene to affect hippocampal volume . Smaller hippocampal volume and reduced grey matter have been observed in otherwise healthy subjects born very preterm . Smaller hippocampal volume has also been reported in healthy adolescents following perinatal asphyxia , and long-term reductions of the grey matter in the amygdala have been observed in children with neonatal hypoxia– ischaemia . Hence, it is plausible that pre- and perinatal complications affect brain structure abnormalities associated with bipolar disorder.

The aim of the current study was to investigate the relationship between pre- and perinatal trauma and brain structure volumes in patients with bipolar disorder. Specifically, we studied the relationship between two measures of pre/perinatal trauma [i.e. an established composite severe OCs score comprising complications occurring throughout the whole preand perinatal period , and a diagnosis of perinatal asphyxia, a distinct complication shown by animal models to cause long-term brain abnormalities ], and three brain volumes either previously reported to be associated with OCs in schizophrenia or associated with bipolar disorder . We hypothesized that perinatal asphyxia and severe OCs would be associated with smaller hippocampus and amygdala volumes, and with larger ventricular volumes, in patients with bipolar disorder, and that the associations would be stronger in those with psychotic than in those with non-psychotic disorder. This latter prediction is based on the findings of more pronounced brain abnormalities and cognitive impairments in the psychotic than non-psychotic form of bipolar disorder. In addition, psychotic bipolar disorder may be more similar to schizophrenia, a disorder in which patients with OCs show more pronounced brain abnormalities than patients without such complications . To our knowledge, this is the first study to explore the association between hypoxia-related OCs, in particular perinatal asphyxia, and neuroanatomy in bipolar disorder.We found that perinatal asphyxia and severe OCs were related to smaller amygdala and hippocampal volume in patients with bipolar disorder. Whereas patients with psychotic bipolar disorder showed reduced amygdala volume following perinatal asphyxia, patients with non-psychotic bipolar disorder showed reduced hippocampal volume following perinatal asphyxia and severe OCs, after adjustment for multiple comparisons, and controlling for the effects of age, sex, ICV and medication use. To the best of our knowledge, this is the first study to investigate associations between hypoxia-related pre- and perinatal complications and brain MRI morphometry in bipolar disorder. Our findings indicate that perinatal hypoxic brain trauma is of importance for the adult brain morphology in bipolar disorder, and may thus be a neurodevelopmental factor of importance to disease development. This concurs to some extent with large scale epidemiological studies that report lower birth weight , specific OCs and premature birth to increase the risk for bipolar disorder or affective psychosis. Indeed, we have in a subject sample overlapping with the current study previously demonstrated lower birth weight to correlate with smaller brain cortical surface area in patients across the psychosis spectrum as well as healthy controls . The results from the current study expand on this by demonstrating distinct associations between specific hypoxia-related pre- and perinatal complications and sub-cortical structures, known to be vulnerable to perinatal hypoxia ,in patients with bipolar disorder. As such, the current findings to some extent support the speculation by Nosarti et al. that there may exist a neurodevelopmental subtype of bipolar disorder. Within the whole group of bipolar disorder patients, we found perinatal asphyxia to be significantly associated with smaller left amygdala volume. The amygdala is involved in emotion processing and regulation, disturbances of which are core features of bipolar disorder . Altered amygdala function related to emotion-processing tasks has repeatedly been reported from functional MRI studies in patients with bipolar disorder .